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1.
Physiol Res ; 73(2): 285-294, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38710059

This study aimed to determine whether electrical stimulation-based twitch exercise is effective in inhibiting the progression of immobilization-induced muscle fibrosis. 19 Wistar rats were randomly divided into a control group (n=6), an immobilization group (n=6; with immobilization only), and a Belt group (n=7; with immobilization and twitch exercise through the belt electrode device, beginning 2 weeks after immobilization). The bilateral soleus muscles were harvested after the experimental period. The right soleus muscles were used for histological analysis, and the left soleus muscles were used for biochemical and molecular biological analysis. As a result, in the picrosirius red images, the perimysium and endomysium were thicker in both the immobilization and Belt groups compared to the control group. However, the perimysium and endomysium thickening were suppressed in the Belt group. The hydroxyproline content and alpha-SMA, TGF-beta1, and HIF-1alpha mRNA expressions were significantly higher in the immobilization and belt groups than in the control group. These expressions were significantly lower in the Belt group than in the immobilization group. The capillary-to-myofiber ratio and the mRNA expressions of VEGF and PGC-1alpha were significantly lower in the immobilization and belt groups than in the control group, these were significantly higher in the Belt group than in the immobilization group. From these results, Electrical stimulation-based twitch exercise using the belt electrode device may prevent the progression of immobilization-induced muscle fibrosis caused by downregulating PGC-1alpha/VEGF pathway, we surmised that this intervention strategy might be effective against the progression of muscle contracture. Keywords: Immobilization, Skeletal muscle, Fibrosis, Electrical stimulation-based twitch exercise, PGC-1alpha/VEGF pathway.


Down-Regulation , Fibrosis , Muscle, Skeletal , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Physical Conditioning, Animal , Rats, Wistar , Vascular Endothelial Growth Factor A , Animals , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Male , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/genetics , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Rats , Physical Conditioning, Animal/physiology , Signal Transduction/physiology , Electric Stimulation , Electric Stimulation Therapy/methods , Disease Progression , Muscular Diseases/metabolism , Muscular Diseases/pathology , Muscular Diseases/prevention & control , Muscular Diseases/etiology
2.
Biomed Environ Sci ; 37(4): 367-376, 2024 Apr 20.
Article En | MEDLINE | ID: mdl-38727159

Objective: This study aimed to clarify the intervention effect of salidroside (SAL) on lung injury caused by PM 2.5 in mice and illuminate the function of SIRT1-PGC-1ɑ axis. Methods: Specific pathogen-free (SPF) grade male C57BL/6 mice were randomly assigned to the following groups: control group, SAL group, PM 2.5 group, SAL+PM 2.5 group. On the first day, SAL was given by gavage, and on the second day, PM 2.5 suspension was given by intratracheal instillation. The whole experiment consist of a total of 10 cycles, lasting 20 days. At the end of treatment, blood samples and lung tissues were collected and analyzed. Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy. The expression of inflammatory, antioxidants, apoptosis, and SIRT1-PGC-1ɑ proteins were detected by Western blotting. Results: Exposure to PM 2.5 leads to obvious morphological and pathologica changes in the lung of mice. PM 2.5 caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1, Nrf2, SOD2, SIRT1 and PGC-1ɑ, and an increase in the protein expressions of IL-6, IL-1ß, Bax, caspase-9 and cleaved caspase-3. However, SAL reversed the aforementioned changes caused by PM 2.5 by activating the SIRT1-PGC-1α pathway. Conclusion: SAL can activate SIRT1-PGC-1ɑ to ameliorate PM 2.5-induced lung injury.


Glucosides , Lung Injury , Mice, Inbred C57BL , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Phenols , Sirtuin 1 , Animals , Glucosides/pharmacology , Glucosides/therapeutic use , Sirtuin 1/metabolism , Sirtuin 1/genetics , Male , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Mice , Lung Injury/drug therapy , Particulate Matter/toxicity , Particulate Matter/adverse effects , Particle Size , Lung/drug effects , Lung/pathology , Lung/metabolism
3.
Sci Rep ; 14(1): 10143, 2024 05 02.
Article En | MEDLINE | ID: mdl-38698042

Sirtuin3 (SIRT3), a mitochondrial deacetylase, has been shown to be involved in various kidney diseases. In this study, we aimed to clarify the role of SIRT3 in cyclosporine-induced nephrotoxicity and the associated mitochondrial dysfunction. Madin-Darby canine kidney (MDCK) cells were transfected with Flag-tagged SIRT3 for SIRT3 overexpression or SIRT3 siRNA for the inhibition of SIRT3. Subsequently, the cells were treated with cyclosporine A (CsA) or vehicle. Wild-type and SIRT3 knockout (KO) mice were randomly assigned to receive cyclosporine A or olive oil. Furthermore, SIRT3 activator, honokiol, was treated alongside CsA to wild type mice. Our results revealed that CsA treatment inhibited mitochondrial SIRT3 expression in MDCK cells. Inhibition of SIRT3 through siRNA transfection exacerbated apoptosis, impaired the expression of the AMP-activated protein kinase-peroxisome proliferator-activated receptor gamma coactivator 1 alpha (AMPK-PGC1α) pathway, and worsened mitochondrial dysfunction induced by CsA treatment. Conversely, overexpression of SIRT3 through Flag-tagged SIRT3 transfection ameliorated apoptosis, increased the expression of mitochondrial superoxide dismutase 2, and restored the mitochondrial regulator pathway, AMPK-PGC1α. In SIRT3 KO mice, CsA treatment led to aggravated kidney dysfunction, increased kidney tubular injury, and accumulation of oxidative end products indicative of oxidative stress injury. Meanwhile, SIRT3 activation in vivo significantly mitigated these adverse effects, improving kidney function, reducing oxidative stress markers, and enhancing mitochondrial health following CsA treatment. Overall, our findings suggest that SIRT3 plays a protective role in alleviating mitochondrial dysfunction caused by CsA through the activation of the AMPK-PGC1α pathway, thereby preventing further kidney injury.


Apoptosis , Cyclosporine , Mice, Knockout , Mitochondria , Oxidative Stress , Sirtuin 3 , Animals , Sirtuin 3/metabolism , Sirtuin 3/genetics , Cyclosporine/adverse effects , Cyclosporine/toxicity , Cyclosporine/pharmacology , Mitochondria/metabolism , Mitochondria/drug effects , Mice , Dogs , Apoptosis/drug effects , Oxidative Stress/drug effects , AMP-Activated Protein Kinases/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Madin Darby Canine Kidney Cells , Kidney Diseases/chemically induced , Kidney Diseases/metabolism , Kidney Diseases/prevention & control , Kidney Diseases/pathology , Kidney Diseases/genetics , Kidney/pathology , Kidney/drug effects , Kidney/metabolism , Mice, Inbred C57BL , Male , Signal Transduction/drug effects
4.
J Transl Med ; 22(1): 419, 2024 May 03.
Article En | MEDLINE | ID: mdl-38702818

BACKGROUND: Glioblastoma is an aggressive brain tumor linked to significant angiogenesis and poor prognosis. Anti-angiogenic therapies with vascular endothelial growth factor receptor 2 (VEGFR2) inhibition have been investigated as an alternative glioblastoma treatment. However, little is known about the effect of VEGFR2 blockade on glioblastoma cells per se. METHODS: VEGFR2 expression data in glioma patients were retrieved from the public database TCGA. VEGFR2 intervention was implemented by using its selective inhibitor Ki8751 or shRNA. Mitochondrial biogenesis of glioblastoma cells was assessed by immunofluorescence imaging, mass spectrometry, and western blot analysis. RESULTS: VEGFR2 expression was higher in glioma patients with higher malignancy (grade III and IV). VEGFR2 inhibition hampered glioblastoma cell proliferation and induced cell apoptosis. Mass spectrometry and immunofluorescence imaging showed that the anti-glioblastoma effects of VEGFR2 blockade involved mitochondrial biogenesis, as evidenced by the increases of mitochondrial protein expression, mitochondria mass, mitochondrial oxidative phosphorylation (OXPHOS), and reactive oxygen species (ROS) production, all of which play important roles in tumor cell apoptosis, growth inhibition, cell cycle arrest and cell senescence. Furthermore, VEGFR2 inhibition exaggerated mitochondrial biogenesis by decreased phosphorylation of AKT and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), which mobilized PGC1α into the nucleus, increased mitochondrial transcription factor A (TFAM) expression, and subsequently enhanced mitochondrial biogenesis. CONCLUSIONS: VEGFR2 blockade inhibits glioblastoma progression via AKT-PGC1α-TFAM-mitochondria biogenesis signaling cascade, suggesting that VEGFR2 intervention might bring additive therapeutic values to anti-glioblastoma therapy.


Apoptosis , Cell Proliferation , Glioblastoma , Mitochondria , Organelle Biogenesis , Vascular Endothelial Growth Factor Receptor-2 , Humans , Glioblastoma/pathology , Glioblastoma/metabolism , Glioblastoma/drug therapy , Vascular Endothelial Growth Factor Receptor-2/metabolism , Cell Proliferation/drug effects , Mitochondria/metabolism , Mitochondria/drug effects , Cell Line, Tumor , Apoptosis/drug effects , Reactive Oxygen Species/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Brain Neoplasms/pathology , Brain Neoplasms/metabolism , Brain Neoplasms/drug therapy , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects
5.
J Diabetes Res ; 2024: 5511454, 2024.
Article En | MEDLINE | ID: mdl-38736904

Adipose tissue dysfunction is seen among obese and type 2 diabetic individuals. Adipocyte proliferation and hypertrophy are the root causes of adipose tissue expansion. Solute carrier family 25 member 28 (SLC25A28) is an iron transporter in the inner mitochondrial membrane. This study is aimed at validating the involvement of SLC25A28 in adipose accumulation by tail vein injection of adenovirus (Ad)-SLC25A28 and Ad-green fluorescent protein viral particles into C57BL/6J mice. After 16 weeks, the body weight of the mice was measured. Subsequently, morphological analysis was performed to establish a high-fat diet (HFD)-induced model. SLC25A28 overexpression accelerated lipid accumulation in white and brown adipose tissue (BAT), enhanced body weight, reduced serum triglyceride (TG), and impaired serum glucose tolerance. The protein expression level of lipogenesis, lipolysis, and serum adipose secretion hormone was evaluated by western blotting. The results showed that adipose TG lipase (ATGL) protein expression was reduced significantly in white and BAT after overexpression SLC25A28 compared to the control group. Moreover, SLC25A28 overexpression inhibited the BAT formation by downregulating UCP-1 and the mitochondrial biosynthesis marker PGC-1α. Serum adiponectin protein expression was unregulated, which was consistent with the expression in inguinal white adipose tissue (iWAT). Remarkably, serum fibroblast growth factor (FGF21) protein expression was negatively related to the expansion of adipose tissue after administrated by Ad-SLC25A28. Data from the current study indicate that SLC25A28 overexpression promotes diet-induced obesity and accelerates lipid accumulation by regulating hormone secretion and inhibiting lipolysis in adipose tissue.


Adipogenesis , Adipose Tissue, Brown , Adipose Tissue, White , Diet, High-Fat , Lipase , Mice, Inbred C57BL , Animals , Mice , Male , Adipose Tissue, Brown/metabolism , Adipose Tissue, White/metabolism , Lipase/metabolism , Lipase/genetics , Obesity/metabolism , Lipolysis , Uncoupling Protein 1/metabolism , Fibroblast Growth Factors/metabolism , Cation Transport Proteins/metabolism , Cation Transport Proteins/genetics , Adipocytes/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Lipogenesis , Acyltransferases
6.
Eur J Histochem ; 68(2)2024 May 13.
Article En | MEDLINE | ID: mdl-38742403

Chronic kidney disease (CKD) is a leading public health issue associated with high morbidity worldwide. However, there are only a few effective therapeutic strategies for CKD. Emodin, an anthraquinone compound from rhubarb, can inhibit fibrosis in tissues and cells. Our study aims to investigate the antifibrotic effect of emodin and the underlying molecular mechanism. A unilateral ureteral obstruction (UUO)-induced rat model was established to evaluate the effect of emodin on renal fibrosis development. Hematoxylin and eosin staining, Masson's trichrome staining, and immunohistochemistry staining were performed to analyze histopathological changes and fibrotic features after emodin treatment. Subsequently, a transforming growth factor-beta 1 (TGF-ß1)-induced cell model was used to assess the inhibition of emodin on cell fibrosis in vitro. Furthermore, Western blot analysis and real-time quantitative reverse transcription-polymerase chain reaction were performed to validate the regulatory mechanism of emodin on renal fibrosis progression. As a result, emodin significantly improved histopathological abnormalities in rats with UUO. The expression of fibrosis biomarkers and mitochondrial biogenesis-related proteins also decreased after emodin treatment. Moreover, emodin blocked TGF-ß1-induced fibrotic phenotype, lipid accumulation, and mitochondrial homeostasis in NRK-52E cells. Conversely, peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α) silencing significantly reversed these features in emodin-treated cells. Collectively, emodin plays an important role in regulating PGC-1α-mediated mitochondria function and energy homeostasis. This indicates that emodin exhibits great inhibition against renal fibrosis and acts as a promising inhibitor of CKD.


Emodin , Fibrosis , Mitochondria , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Renal Insufficiency, Chronic , Animals , Emodin/pharmacology , Emodin/therapeutic use , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/pathology , Fibrosis/drug therapy , Mitochondria/drug effects , Mitochondria/metabolism , Male , Rats , Rats, Sprague-Dawley , Homeostasis/drug effects , Kidney/pathology , Kidney/drug effects , Kidney/metabolism , Ureteral Obstruction/pathology , Ureteral Obstruction/drug therapy , Transforming Growth Factor beta1/metabolism , Cell Line
7.
Proc Natl Acad Sci U S A ; 121(19): e2313590121, 2024 May 07.
Article En | MEDLINE | ID: mdl-38683978

Myokines and exosomes, originating from skeletal muscle, are shown to play a significant role in maintaining brain homeostasis. While exercise has been reported to promote muscle secretion, little is known about the effects of neuronal innervation and activity on the yield and molecular composition of biologically active molecules from muscle. As neuromuscular diseases and disabilities associated with denervation impact muscle metabolism, we hypothesize that neuronal innervation and firing may play a pivotal role in regulating secretion activities of skeletal muscles. We examined this hypothesis using an engineered neuromuscular tissue model consisting of skeletal muscles innervated by motor neurons. The innervated muscles displayed elevated expression of mRNAs encoding neurotrophic myokines, such as interleukin-6, brain-derived neurotrophic factor, and FDNC5, as well as the mRNA of peroxisome-proliferator-activated receptor γ coactivator 1α, a key regulator of muscle metabolism. Upon glutamate stimulation, the innervated muscles secreted higher levels of irisin and exosomes containing more diverse neurotrophic microRNAs than neuron-free muscles. Consequently, biological factors secreted by innervated muscles enhanced branching, axonal transport, and, ultimately, spontaneous network activities of primary hippocampal neurons in vitro. Overall, these results reveal the importance of neuronal innervation in modulating muscle-derived factors that promote neuronal function and suggest that the engineered neuromuscular tissue model holds significant promise as a platform for producing neurotrophic molecules.


Brain-Derived Neurotrophic Factor , Exosomes , Muscle, Skeletal , Exosomes/metabolism , Animals , Muscle, Skeletal/metabolism , Muscle, Skeletal/innervation , Brain-Derived Neurotrophic Factor/metabolism , Mice , Fibronectins/metabolism , Motor Neurons/metabolism , Interleukin-6/metabolism , MicroRNAs/metabolism , MicroRNAs/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Neurons/metabolism , Nerve Growth Factors/metabolism , Myokines
8.
J Hazard Mater ; 471: 134331, 2024 Jun 05.
Article En | MEDLINE | ID: mdl-38677116

Recent studies are identified the mitochondria as critical targets of 2, 2', 4, 4'-tetrabromodiphenyl ether (PBDE-47) induced neurotoxicity. This study aimed at examining the impact of PBDE-47 exposure on mitochondrial translation, and its subsequent effect on PBDE-47 neurotoxicity. The Sprague-Dawley (SD) rat model and neuroendocrine pheochromocytoma (PC12) cells were adopted for the measurements of mitochondrial ATP levels, mitochondrial translation products, and expressions of important mitochondrial regulators, such as required meiotic nuclear division 1 (RMND1), estrogen-related receptor α (ERRα), and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α). To delve into the role of PGC-1α/ERRα axis in mitochondrial translation, 2-(4-tert-butylphenyl) benzimidazole (ZLN005) was employed. Both cellular and animal model results shown that PBDE-47 impeded PGC-1α/ERRα axis and mitochondrial translation. PBDE-47 suppressed mitochondrial function in rat hippocampus and PC12 cells by decreasing relative mitochondrial DNA (mtDNA) content, mitochondrial translation products, and mitochondrial ATP levels. Particularly, ZLN005 reversed PBDE-47 neurotoxicity by enhancing mitochondrial translation through activation of PGC-1α/ERRα axis, yet suppressing PGC-1α with siRNA attenuates its neuroprotective effect in vitro. In conclusion, this work highlights the importance of mitochondrial translation in PBDE-47 neurotoxicity by presenting results from cellular and animal models and suggests a potential therapeutic approach through activation of PGC-1α/ERRα axis. ENVIRONMENTAL IMPLICATION: PBDEs have attracted extensive attention because of their high lipophilicity, persistence, and detection levels in various environmental media. Increasing evidence has shown that neurodevelopmental disorders in children are associated with PBDE exposure. Several studies have also found that perinatal PBDE exposure can cause long-lasting neurobehavioral abnormalities in experimental animals. Our recent studies have also demonstrated the impact of PBDE-47 exposure on mitochondrial biogenesis and dynamics, leading to memory and neurobehavioral deficits. Therefore, we explore whether the pathological mechanism of PBDE-47-induced neurotoxicity involves the regulation of mitochondrial translation through the PGC-1α/ERRα axis.


Halogenated Diphenyl Ethers , Mitochondria , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Rats, Sprague-Dawley , Receptors, Estrogen , Animals , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Halogenated Diphenyl Ethers/toxicity , PC12 Cells , Rats , Mitochondria/drug effects , Mitochondria/metabolism , Receptors, Estrogen/metabolism , ERRalpha Estrogen-Related Receptor , Benzimidazoles/pharmacology , Male , Protein Biosynthesis/drug effects , Neurotoxicity Syndromes/metabolism
9.
Cell Signal ; 119: 111177, 2024 Jul.
Article En | MEDLINE | ID: mdl-38621470

In this study, blueberry anthocyanins extract (BAE) was used to investigate its protective effect on arsenic-induced rat hippocampal neurons damage. Arsenic exposure resulted in elevated levels of oxidative stress, decreased antioxidant capacity and increased apoptosis in rat hippocampal brain tissue and mitochondria. Immunohistochemical results showed that arsenic exposure also significantly decreased the expression of mitochondrial biosynthesis-related factors PGC-1α and TFAM. Treatment with BAE alleviated the decrease in antioxidant capacity, mitochondrial biogenesis related protein PGC-1α/NRF2/TFAM expression, and ATP production of arsenic induced hippocampal neurons in rats, and improved cognitive function in arsenic damaged rats. This study provides new insights into the detoxification effect of anthocyanins on the nervous system toxicity caused by metal exposure in the environment, indicating that anthocyanins may be a natural antioxidant against the nervous system toxicity caused by environmental metal exposure.


Anthocyanins , Arsenic , Blueberry Plants , Hippocampus , Memory Disorders , Mitochondria , NF-E2-Related Factor 2 , Neurons , Oxidative Stress , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Animals , Blueberry Plants/chemistry , Oxidative Stress/drug effects , Hippocampus/metabolism , Hippocampus/drug effects , Arsenic/toxicity , Neurons/drug effects , Neurons/metabolism , Mitochondria/metabolism , Mitochondria/drug effects , Anthocyanins/pharmacology , Rats , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Memory Disorders/chemically induced , Memory Disorders/metabolism , Memory Disorders/drug therapy , NF-E2-Related Factor 2/metabolism , Antioxidants/pharmacology , Male , DNA-Binding Proteins/metabolism , Apoptosis/drug effects , Transcription Factors/metabolism , Rats, Sprague-Dawley , Plant Extracts/pharmacology
10.
Neuropharmacology ; 252: 109950, 2024 Jul 01.
Article En | MEDLINE | ID: mdl-38636727

Effective therapeutic interventions for elderly patients are lacking, despite advances in pharmacotherapy. Methylated urolithin A (mUro A), a modified ellagitannin (ET)-derived metabolite, exhibits anti-inflammatory, antioxidative, and anti-apoptotic effects. Current research has primarily investigated the neuroprotective effects of mUroA in aging mice and explored the underlying mechanisms. Our study used an in vivo aging model induced by d-galactose (D-gal) to show that mUro A notably improved learning and memory, prevented synaptic impairments by enhancing synaptic protein expression and increasing EPSCs, and reduced oxidative damage in aging mice. mUro A alleviated the activation of the NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome, leading to reduced glial cell activity and neuroinflammation in both accelerated aging and naturally senescent mouse models. Moreover, mUroA enhanced the activity of TCA cycle enzymes (PDH, CS, and OGDH), decreased 8-OHdG levels, and raised ATP and NAD+ levels within the mitochondria. At the molecular level, mUro A decreased phosphorylated p53 levels and increased the expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), thus enhancing mitochondrial function. In conclusion, mUro A alleviates cognitive impairment in aging mice by suppressing neuroinflammation through NLRP3 inflammasome inhibition and restoring mitochondrial function via the p53-PGC-1α pathway. This suggests its potential therapeutic agent for brain aging and aging-related diseases.


Aging , Cognitive Dysfunction , Coumarins , Inflammasomes , Mice, Inbred C57BL , Mitochondria , NLR Family, Pyrin Domain-Containing 3 Protein , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Coumarins/pharmacology , Aging/drug effects , Aging/metabolism , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/metabolism , Inflammasomes/metabolism , Inflammasomes/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Mice , Male , Galactose , Neuroprotective Agents/pharmacology , Oxidative Stress/drug effects , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism
11.
Food Funct ; 15(9): 4852-4861, 2024 May 07.
Article En | MEDLINE | ID: mdl-38573228

This study elucidates the mechanism of obesity-related adverse pregnancy outcomes and further investigates the effect of resveratrol on reproductive performance in a short- or long-term HFD-induced obese mouse model. Results show that maternal weight had a significant positive correlation with litter mortality in mice. A long-term HFD increased body weight and litter mortality with decreased expression of uterine cytochrome oxidase 4 (COX4), which was recovered by resveratrol in mice. Moreover, HFD decreased the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factors-1 (Nrf-1), and phosphorylated adenosine 5'-monophosphate (AMP)-activated protein kinase (p-AMPK) and increased the expression of phosphorylated extracellular regulated protein kinases (p-ERK) in the uterus. Resveratrol, a polyphenol that can directly bind to the ERK protein, suppressed the phosphorylation of ERK, increased the expression of p-AMPK, PGC-1α and Nrf-1, and decreased litter mortality in mice.


Diet, High-Fat , Mitochondria , Pregnancy Outcome , Resveratrol , Uterus , Animals , Resveratrol/pharmacology , Female , Pregnancy , Mice , Diet, High-Fat/adverse effects , Mitochondria/drug effects , Mitochondria/metabolism , Uterus/metabolism , Uterus/drug effects , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Mice, Inbred C57BL , Obesity/metabolism , AMP-Activated Protein Kinases/metabolism
12.
Cancer Res ; 84(10): 1630-1642, 2024 May 15.
Article En | MEDLINE | ID: mdl-38588407

Cancer stem/tumor-initiating cells display stress tolerance and metabolic flexibility to survive in a harsh environment with limited nutrient and oxygen availability. The molecular mechanisms underlying this phenomenon could provide targets to prevent metabolic adaptation and halt cancer progression. Here, we showed in cultured cells and live human surgical biopsies of non-small cell lung cancer that nutrient stress drives the expression of the epithelial cancer stem cell marker integrin αvß3 via upregulation of the ß3 subunit, resulting in a metabolic reprogramming cascade that allows tumor cells to thrive despite a nutrient-limiting environment. Although nutrient deprivation is known to promote acute, yet transient, activation of the stress sensor AMP-activated protein kinase (AMPK), stress-induced αvß3 expression via Src activation unexpectedly led to secondary and sustained AMPK activation. This resulted in the nuclear localization of peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC1α) and upregulation of glutamine metabolism, the tricarboxylic acid cycle, and oxidative phosphorylation. Pharmacological or genetic targeting of this axis prevented lung cancer cells from evading the effects of nutrient stress, thereby blocking tumor initiation in mice following orthotopic implantation of lung cancer cells. These findings reveal a molecular pathway driven by nutrient stress that results in cancer stem cell reprogramming to promote metabolic flexibility and tumor initiation. SIGNIFICANCE: Upregulation of integrin αvß3, a cancer stem cell marker, in response to nutrient stress activates sustained AMPK/PGC1α signaling that induces metabolic reprogramming in lung cancer cells to support their survival. See related commentary by Rainero, p. 1543.


Carcinoma, Non-Small-Cell Lung , Integrin alphaVbeta3 , Lung Neoplasms , Up-Regulation , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Animals , Integrin alphaVbeta3/metabolism , Mice , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/genetics , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , AMP-Activated Protein Kinases/metabolism , Stress, Physiological , Nutrients/metabolism , Cell Line, Tumor , Gene Expression Regulation, Neoplastic
13.
Exp Gerontol ; 190: 112428, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38604253

BACKGROUND: Mitochondrial dysregulation in skeletal myocytes is considered a major factor in aged sarcopenia. In this study, we aimed to study the effects of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) on Sestrin2-mediated mechanistic target of rapamycin complex 1 (mTORC1) in aged skeletal muscles. METHODS: C2C12 myoblasts were stimulated by 50 µM 7ß-hydroxycholesterol (7ß-OHC) to observe the changes of DNA damage, mitochondrial membrane potential (Δψm), mitochondrial ROS and PGC-1α protein. The PGC-1α silence in the C2C12 cells was established by siRNA transfection. The levels of DNA damage, Δψm, mitochondrial ROS, Sestrin2 and p-S6K1/S6K1 proteins were observed after the PGC-1α silence in the C2C12 cells. Recombinant Sestrin2 treatment was used to observe the changes of DNA damage, Δψm, mitochondrial ROS and p-S6K1/S6K1 protein in the 7ß-OHC-treated or PGC-1α siRNA-transfected C2C12 cells. Wild-type (WT) mice and muscle-specific PGC-1α conditional knockout (MKO) mice, including young and old, were used to analyse the effects of PGC-1α on muscle function and the levels of Sestrin2 and p-S6K1 in the white gastrocnemius muscles. Recombinant Sestrin2 was administrated to analyse its effects on muscle function in the old WT mice and old MKO mice. RESULTS: 7ß-OHC treatment induced DNA damage, mitochondrial dysfunction and decrease of PGC-1α protein in the C2C12 cells. PGC-1α silence also induced DNA damage and mitochondrial dysfunction in the C2C12 cells. Additionally, PGC-1α silence or 7ß-OHC treatment decreased the levels of Sestrin2 and p-S6K1/S6K1 protein in the C2C12 cells. Recombinant Sestrin2 treatment significantly improved the DNA damage and mitochondrial dysfunction in the 7ß-OHC-treated or PGC-1α siRNA-transfected C2C12 cells. At the same age, muscle-specific PGC-1α deficiency aggravated aged sarcopenia and decreased the levels of Sestrin2 and p-S6K1 in the white gastrocnemius muscles when compared to the WT mice. Recombinant Sestrin2 treatment improved muscle function and increased p-S6K1 levels in the old two genotypes. CONCLUSION: This research demonstrates that PGC-1α participates in regulating mitochondrial function in aged sarcopenia through effects on the Sestrin2-mediated mTORC1 pathway.


DNA Damage , Mechanistic Target of Rapamycin Complex 1 , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Ribosomal Protein S6 Kinases, 90-kDa , Sarcopenia , Sestrins , Animals , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Mice , Mechanistic Target of Rapamycin Complex 1/metabolism , Sarcopenia/metabolism , Mice, Knockout , Membrane Potential, Mitochondrial , Reactive Oxygen Species/metabolism , Aging/physiology , Aging/metabolism , Signal Transduction , Nuclear Proteins/metabolism , Nuclear Proteins/genetics , Male , Muscle, Skeletal/metabolism , Cell Line , Mitochondria/metabolism , Peroxidases/metabolism , Mice, Inbred C57BL , Myoblasts/metabolism
14.
PLoS One ; 19(4): e0301036, 2024.
Article En | MEDLINE | ID: mdl-38625956

PURPOSE: This study aims to investigate the protective mechanism of dihydromyricetin PLGA nanoparticles (DMY-PLGA NPs) against myocardial ischemia-reperfusion injury (MIRI) in vitro and the improvement of oral bioavailability in vivo. METHODS: DMY-PLGA NPs was prepared and characterized by emulsifying solvent volatilization, and the oxidative stress model of rat H9c2 cardiomyocyte induced by H2O2 was established. After administration, cell survival rate, lactate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide dismutase (SOD) were detected, and the expressions of PGC1α and PPARα were detected by western blot (WB). At the same time, the pharmacokinetics in rats were studied to explore the improvement of bioavailability. RESULTS: DMY-PLGA NPs can significantly increase cell survival rate, decrease LDH and MDA content, increase SOD content and PGC1α、PPARα protein expression. Compared with DMY, the peak time of DMY-PLGA NPs was extended (P<0.1), and the bioavailability was increased by 2.04 times. CONCLUSION: DMY-PLGA NPs has a significant protective effect on H9c2 cardiomyocytes, which promotes the absorption of DMY and effectively improves bioavailability.


Flavonols , Hydrogen Peroxide , PPAR alpha , Rats , Animals , Hydrogen Peroxide/metabolism , PPAR alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Oxidative Stress , Myocardium/metabolism , Myocytes, Cardiac/metabolism , Superoxide Dismutase/metabolism , Apoptosis
15.
J Cell Mol Med ; 28(8): e18051, 2024 Apr.
Article En | MEDLINE | ID: mdl-38571282

We previously showed that mice with knockout in the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) gene encoding the PGC-1α protein, and nuclear factor erythroid 2 like 2 (NFE2L2) gene, exhibited some features of the age-related macular degeneration (AMD) phenotype. To further explore the mechanism behind the involvement of PGC-1α in AMD pathogenesis we used young (3-month) and old (12-month) mice with knockout in the PPARGC1A gene and age-matched wild-type (WT) animals. An immunohistochemical analysis showed age-dependent different expression of markers of oxidative stress defence, senescence and autophagy in the retinal pigment epithelium of KO animals as compared with their WT counterparts. Multivariate inference testing showed that senescence and autophagy proteins had the greatest impact on the discrimination between KO and WT 3-month animals, but proteins of antioxidant defence also contributed to that discrimination. A bioinformatic analysis showed that PGC-1α might coordinate the interplay between genes encoding proteins involved in antioxidant defence, senescence and autophagy in the ageing retina. These data support importance of PGC-1α in AMD pathogenesis and confirm the utility of mice with PGC-1α knockout as an animal model to study AMD pathogenesis.


Antioxidants , Macular Degeneration , Mice , Animals , Antioxidants/metabolism , Mitochondria/metabolism , Oxidative Stress , Aging , Macular Degeneration/metabolism , Autophagy/genetics , Retinal Pigment Epithelium/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism
16.
BMC Surg ; 24(1): 129, 2024 Apr 27.
Article En | MEDLINE | ID: mdl-38678284

BACKGROUND: Mitochondria dysfunction is one of the major causes of insulin resistance, and other countless complications of obesity. PGC-1α, and UCP-2 play key roles in energy expenditure regulation in the mitochondrial thermogenesis. However, the effects of bariatric surgery on the level of PGC-1α and UCP-2 and their relationships are unclear. OBJECTIVE: This study aimed to investigate the effect of bariatric surgery on key pathways in energy, and to assess the potential predictive role of body composition and metabolic parameters in this regard. SETTINGS: Hazrat-e Rasool General Hospital, Center of Excellence of International Federation for Surgery of Obesity. METHODS: This prospective cohort study was carried out on 45 patients with morbid obesity who underwent Roux-en-Y gastric bypass surgery. The patients have evaluated three-time points at baseline, three, and six months after the surgery. Body composition components, the levels of PGC-1α, UCP-2, and metabolic parameters were measured three times during this study. RESULTS: Significant changes in TWL%, EBMIL%, and metabolic lab tests were observed at three- and six months post-surgery (P < 0.001). The PGC-1α and UCP-2 had a significant increase three and then six-month post-operation compared with the baseline (P < 0.001). Moreover, multivariate linear regression analysis identified that the changing trend of PGC-1α was associated with insulin, uric Acid, HOMA-IR, fat mass and trunk fat mass. UCP-2 was associated with TSH, AST, fat mass and FFM. CONCLUSIONS: Bariatric surgery has been shown to have a positive effect on UCP-2 and PGC-1α levels, as well as body composition and metabolic parameters. As a result, it is believed that bariatric surgery could improve thermogenesis and energy expenditure by enhancing mitochondrial biogenesis and function. However, further studies are needed to fully understand the precise mechanisms and possible causal relationship.


Biomarkers , Energy Metabolism , Obesity, Morbid , Uncoupling Protein 2 , Humans , Female , Prospective Studies , Energy Metabolism/physiology , Male , Adult , Biomarkers/metabolism , Biomarkers/blood , Obesity, Morbid/surgery , Obesity, Morbid/metabolism , Uncoupling Protein 2/metabolism , Middle Aged , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Bariatric Surgery , Gastric Bypass , Body Composition
17.
Ecotoxicol Environ Saf ; 276: 116259, 2024 May.
Article En | MEDLINE | ID: mdl-38581905

Gestational cadmium exposure increases the risk of preeclampsia. Placenta mitophagy was activated in preeclampsia. The aim of present study was to explore the mechanism of cadmium-induced mitophagy activation and its association with preeclampsia. Mitophagy markers expression levels were detected by quantitative real-time PCR, Western blot, immunofluorescence and immunochemistry in preeclampsia placenta. JEG3 cells were treated with CdCl2, iopanoic acid (IOP), 3-methyladenine and PGC1α SiRNA to verify mechanism of cadmium-induced mitophagy. Mitophagy marker LC3BII/I and P62 expression were increased and mitochondrial membrane receptor protein TOM20 and FUNDC1 expression were decreased in preeclampsia placenta as compared with that in normotension control. Mitophagy marker LC3BII/I and P62 expression were increased and TOM20 and FUNDC1 expression was decreased in CdCl2-treated JEG3 cells. Meanwhile, mitochondrial biogenesis regulator, PGC1α expression was decreased in preeclampsia and CdCl2-treated JEG3 cells. The expressions of LC3B and P62 were increased and the expressions of TOM20, FUNDC1 and PGC1α were decreased in IOP-treated cell. PGC1α SiRNA transfection led to increased expression of LC3BII/I and P62 and decreased expression of TOM20 and FUNDC1. The expression of sFlt1 was increased in preeclampsia placenta, CdCl2-treated cells, in IOP-treated cells and in PGC1α SiRNA transfected cells. 3-methyladenine treatment protected the increased expression of sFlt1 in CdCl2-treated cells, in IOP-treated cells and in PGC1α SiRNA transfected cells. Meanwhile, co-treatment of cadmium and IOP or PGC1αSiRNA led to a reduce expressions of OPA1, MFN1, MFN2 and FUNDC1 as compared to cadmium-treated, IOP-treated and PGC1α SiRNA-treated cells. These results elucidated that maternal cadmium exposure activated placenta mitophagy through downregulation of thyroid hormone receptor signal mediated decreased expression of PGC1α and was associated with the occurrence of preeclampsia.


Mitophagy , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Placenta , Pre-Eclampsia , Receptors, Thyroid Hormone , Humans , Pre-Eclampsia/chemically induced , Female , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Pregnancy , Mitophagy/drug effects , Placenta/drug effects , Placenta/metabolism , Receptors, Thyroid Hormone/genetics , Receptors, Thyroid Hormone/metabolism , Cadmium/toxicity , Down-Regulation/drug effects , Adult , Signal Transduction/drug effects
18.
J Ethnopharmacol ; 330: 118150, 2024 Aug 10.
Article En | MEDLINE | ID: mdl-38631487

ETHNOPHARMACOLOGICAL RELEVANCE: JiaWei DaChaiHu is composed of Bupleurum chinense, Scutellaria baicalensis, Pinellia ternata, Paeonia lactiflora, Zingiber officinaleRoscoe, Poncirus tuifoliata, Rheum palmatum L., Curcumae Radix, Herba Lysimachiae, Ziziphus. JiaWei DaChaiHu is one of the most common traditional Chinese medicines for the treatment of depression. AIM OF THE STUDY: The chronic unpredictable mild stress (CUMS) has been shown to promote atherosclerosis (AS). Dachaihu has been widely used in traditional Chinese medicine and has been known to exert distinct pharmacological effects. This investigation aims to examine the therapeutic effect of Jiawei Dachaihu extract on AS animal models with CUMS. METHODS: AS-CUMS mice model was established by Apoe-/- mice. Mice were treated with Jiawei Dachaihu. Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C) levels were measured using ELISA kits. Aortic tissue pathologic changes detected by oil red O staining. Mice behavioral changes detected by sucrose preference test and sucrose preference test. The relative mRNA expression levels of CRH, ND1, and TFAM were determined by qRT-PCR. 5-HT1A, BDNF, LON, TFAM, PGC-1α, and SIRT1 protein expression determined by western blotting. ATP content detected by ATP kits. RESULTS: The treatment with Jiawei Dachaihu extract alleviated the veins plaque and reduced stress signs in vitro and in vivo. It increased the ATP and HDL-C levels while decreased the TC, TG, LDL-C levels. Jiawei Dachaihu extract treatment upregulated Lon, SIRT1, TFAM, PGC-1α, BDNF, and 5-HT1A protein expression and regained mitochondrial function. CONCLUSION: Jiawei Dachaihu extract could alleviate AS and reduce CUMS by upregulating the SIRT1/PGC-1α signaling and promoted its crosstalk with Lon protein to maintain mitochondrial stability.


Atherosclerosis , Drugs, Chinese Herbal , Mitochondria , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Signal Transduction , Sirtuin 1 , Stress, Psychological , Animals , Atherosclerosis/drug therapy , Sirtuin 1/metabolism , Sirtuin 1/genetics , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Male , Signal Transduction/drug effects , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Mice , Stress, Psychological/drug therapy , Mitochondria/drug effects , Mitochondria/metabolism , Mice, Inbred C57BL , Disease Models, Animal , Transcription Factors/metabolism , Transcription Factors/genetics , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Mice, Knockout, ApoE
19.
Discov Med ; 36(183): 788-798, 2024 Apr.
Article En | MEDLINE | ID: mdl-38665027

BACKGROUND: High-salt diet (HSD) is a pivotal risk factor for osteoporosis (OP). Accumulating evidence has supported that tauroursodeoxycholic acid (TUDCA), a naturally produced hydrophilic bile acid, exerts positive effects on the treatment of OP. This study is committed to shedding light on the impacts of TUDCA on high salt-treated osteoblasts and probing into its underlying mechanisms of action. METHODS: Cell counting kit-8 (CCK-8) assay was used to determine the viability of osteoblasts. Alkaline phosphatase (ALP) staining and Alizarin red S (ARS) staining were used to measure osteoblast differentiation. Reverse transcription-quantitative PCR (RT-qPCR) and western blot were used to examine the expression of osteogenic markers. Western blot was also used to analyze the expression of superoxide dismutase-2 (SOD2), peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α), and NADPH oxidase 1 (NOX1). The production of reactive oxygen species (ROS) was evaluated via dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay. Following PGC-1α knockdown in TUDCA-pretreated osteoblasts exposed to NaCl, the aforementioned functional experiments were implemented again. RESULTS: MC3T3-E1 cell viability was not significantly impacted by increasing concentrations of TUDCA. However, in NaCl-exposed MC3T3-E1 cells, the viability loss, oxidative stress, and decline of differentiation were all dose-dependently obstructed by TUDCA treatment. Moreover, NaCl exposure reduced PGC-1α expression and increased NOX1 expression, which was then reversed by TUDCA. PGC-1α deletion partially abolished the effects of TUDCA on PGC-1α and NOX1, differentiation, and oxidative stress in NaCl-treated osteoblasts. CONCLUSIONS: TUDCA might protect against high salt-induced OP via modulation of NOX1 mediated by PGC-1α.


NADPH Oxidase 1 , Osteoblasts , Oxidative Stress , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Taurochenodeoxycholic Acid , Animals , Mice , Cell Differentiation/drug effects , NADPH Oxidase 1/metabolism , NADPH Oxidase 1/genetics , Osteoblasts/drug effects , Osteoblasts/metabolism , Oxidative Stress/drug effects , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Reactive Oxygen Species/metabolism , Taurochenodeoxycholic Acid/pharmacology
20.
Zhen Ci Yan Jiu ; 49(4): 349-357, 2024 Apr 25.
Article En, Zh | MEDLINE | ID: mdl-38649202

OBJECTIVES: To observe the effect of electroacupuncture (EA) on activation of silent information regulator 1 (Sirt1)/peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)/mitochondrial transcription factor A (TFAM) pathway in type 2 diabetes (T2DM) rats with peripheral neuropathy (DPN) , so as to explore its possible mechanisms underlying improvement of DPN. METHODS: Thirty male SD rats were randomly divided into blank control group (n=8) and DPN model group (n=22) which were further divided into model group (n=8) and EA group (n=8) after successful modeling. The model of T2DM was established by high-fat diet and low-dose intraperitoneal injection of streptozocin (35 mg/kg). For rats of the EA group (anesthetized with isoflurane), EA stimulation (2 Hz/15 Hz, 2 mA) was applied to "Tianshu"(ST25) for 20 min, once daily, 6 times a week for 6 weeks. The blood glucose level, body weight, area under curve (AUC) of glucose tolerance test, and hind-paw mechanical pain threshold and thermal pain threshold were observed. The intra-epidermal nerve fiber density (IENFD) of the hind-foot pad was observed by immunofluorescence staining. The motor nerve conduction velocity (MNCV) of the sciatic nerve was measured by using electrophysiological method. H.E. staining was used to observe the histopathological changes of the sciatic nerve after modeling. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes of the sciatic nerve. The protein expressions of energy-related Sirt1, PGC-1α and TFAM in the sciatic nerve was detected by Western blot. RESULTS: Compared with the blank control group, the model group had a higher blood glucose contents and AUC (P<0.001), a slower MNCV (P<0.01), and a decrease in the body weight and in the mechanical and thermal pain thresholds (P<0.001) and IENFD (P<0.001), and in the expression levels of Sirt1, PGC-1α and TFAM (P<0.05, P<0.01). In contrast to the model group, the EA group had a decrease in the blood glucose contents and AUC (P<0.05, P<0.01), and an increase in mechanical and thermal pain thresholds, MNCV, IENFD, and expression levels of Sirt1, PGC-1α and TFAM proteins (P<0.01, P<0.05). In addition, results of histopathological and ultrastructural changes of the sciatic nerve showed more fragmented and disordered distribution of axons on the transverse section, and extensive separation of myelin and axons, uneven myelin thickness, axonal degeneration and irregular shape in the model group, whereas in the EA group, the axons on the transverse section were relatively more dense and more complete, the myelin sheath of the sciatic nerve was relatively uniform, and the axonal shape was relatively regular with relatively milder lesions. CONCLUSIONS: EA up-regulates the expressions of Sirt1, PGC-1α, TFAM in T2DM rats with DPN, which may be associated with its functions in improving and repairing the injured peripheral nerves in rats with DPN.


Acupuncture Points , Diabetes Mellitus, Type 2 , Electroacupuncture , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Sirtuin 1 , Animals , Humans , Male , Rats , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/therapy , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/genetics , Diabetic Neuropathies/therapy , Diabetic Neuropathies/metabolism , Diabetic Neuropathies/genetics , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Mitochondrial Proteins/metabolism , Mitochondrial Proteins/genetics , Peripheral Nervous System Diseases/therapy , Peripheral Nervous System Diseases/metabolism , Peripheral Nervous System Diseases/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Rats, Sprague-Dawley , Sciatic Nerve/metabolism , Sirtuin 1/metabolism , Sirtuin 1/genetics , Transcription Factors/genetics , Transcription Factors/metabolism
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