Molecular regulators of exercise-mediated insulin sensitivity in non-obese individuals.

Insulin resistance is a significant contributor to the development of type 2 diabetes (T2D) and is associated with obesity, physical inactivity, and low maximal oxygen uptake. While intense and prolonged exercise may have negative effects, physical activity can have a positive influence on cellular metabolism and the immune system. Moderate exercise has been shown to reduce oxidative stress and improve antioxidant status, whereas intense exercise can increase oxidative stress in the short term. The impact of exercise on pro-inflammatory cytokine production is complex and varies depending on intensity and duration. Exercise can also counteract the harmful effects of ageing and inflamm-ageing. This review aims to examine the molecular pathways altered by exercise in non-obese individuals at higher risk of developing T2D, including glucose utilization, lipid metabolism, mitochondrial function, inflammation and oxidative stress, with the potential to improve insulin sensitivity. The focus is on understanding the potential benefits of exercise for improving insulin sensitivity and providing insights for future targeted interventions before onset of disease.

Intrinsic structural vulnerability in the hydrophobic core induces species-specific aggregation of canine SOD1 with degenerative myelopathy-linked E40K mutation.

Canine degenerative myelopathy (DM), a fatal neurodegenerative disease in dogs, shares clinical and genetic features with amyotrophic lateral sclerosis, a human motor neuron disease. Mutations in the SOD1 gene encoding Cu/Zn superoxide dismutase (SOD1) cause canine DM and a subset of inherited human amyotrophic lateral sclerosis. The most frequent DM causative mutation is homozygous E40K mutation, which induces the aggregation of canine SOD1 but not of human SOD1. However, the mechanism through which canine E40K mutation induces species-specific aggregation of SOD1 remains unknown. By screening human/canine chimeric SOD1s, we identified that the humanized mutation of the 117th residue (M117L), encoded by exon 4, significantly reduced aggregation propensity of canine SOD1E40K. Conversely, introducing a mutation of leucine 117 to methionine, a residue homologous to canine, promoted E40K-dependent aggregation in human SOD1. M117L mutation improved protein stability and reduced cytotoxicity of canine SOD1E40K. Furthermore, crystal structural analysis of canine SOD1 proteins revealed that M117L increased the packing within the hydrophobic core of the ß-barrel structure, contributing to the increased protein stability. Our findings indicate that the structural vulnerability derived intrinsically from Met 117 in the hydrophobic core of the ß-barrel structure induces E40K-dependent species-specific aggregation in canine SOD1.

Identification of quantitative trait loci and candidate genes for grain superoxide dismutase activity in wheat.

BACKGROUND: Superoxide dismutase (SOD) can greatly scavenge reactive oxygen species (ROS) in plants. SOD activity is highly related to plant stress tolerance that can be improved by overexpression of SOD genes. Identification of SOD activity-related loci and potential candidate genes is essential for improvement of grain quality in wheat breeding. However, the loci and candidate genes for relating SOD in wheat grains are largely unknown. In the present study, grain SOD activities of 309 recombinant inbred lines (RILs) derived from the 'Berkut' × 'Worrakatta' cross were assayed by photoreduction method with nitro-blue tetrazolium (NBT) in four environments. Quantitative trait loci (QTL) of SOD activity were identified using inclusive composite interval mapping (ICIM) with the genotypic data of 50 K single nucleotide polymorphism (SNP) array. RESULTS: Six QTL for SOD activity were mapped on chromosomes 1BL, 4DS, 5AL (2), and 5DL (2), respectively, explaining 2.2 ~ 7.4% of the phenotypic variances. Moreover, QSOD.xjau-1BL, QSOD.xjau-4DS, QSOD.xjau-5 A.1, QSOD.xjau-5 A.2, and QSOD.xjau-5DL.2 identified are likely to be new loci for SOD activity. Four candidate genes TraesCS4D01G059500, TraesCS5A01G371600, TraesCS5D01G299900, TraesCS5D01G343100LC, were identified for QSOD.xjau-4DS, QSOD.xjau-5AL.1, and QSOD.xjau-5DL.1 (2), respectively, including three SOD genes and a gene associated with SOD activity. Based on genetic effect analysis, this can be used to identify desirable alleles and excellent allele variations in wheat cultivars. CONCLUSION: These candidate genes are annotated for promoting SOD production and inhibiting the accumulation of ROS during plant growth. Therefore, lines with high SOD activity identified in this study may be preferred for future wheat breeding.

Superoxide dismutase: a key target for the neuroprotective effects of curcumin.

Over the past few years, the prevalence of neurodegenerative diseases (NDD) has increased dramatically. The community health system is burdened by the high healthcare costs associated with NDD. Superoxide dismutase (SOD) is a type of metalloenzyme that possesses a distinct characteristic of protecting the body from oxidative stress through antioxidants. In this way, SOD supplementation may activate the endogenous antioxidant mechanism in various pathological conditions and could be used to neutralize free radical excess. Several factors are responsible for damaging DNA and RNA in the body, including the overproduction of reactive species, particularly reactive oxygen species (ROS) and reactive nitrogen species (RNS). Excessive ROS/RNS have deleterious effects on mitochondria and their metabolic processes, mainly through increased mitochondrial proteins, lipids and DNA oxidation. Studies have shown that oxidative stress is implicated in the etiology of many diseases, including NDD. It is thought that anti-inflammatory compounds, particularly phytochemicals, can interfere with these pathways and regulate inflammation. Extensive experimental and clinical research has proven that curcumin (Cur) has anti-inflammatory and anti-neurologic properties. In this review, we have compiled the available data on Cur's anti-inflammatory properties, paying special attention to its therapeutic impact on NDD through SOD.

Gold nanoparticles (AuNPs) decrease the viability of cervical cancer cells by inducing the BAX gene and activating antioxidant enzymes.

BACKGROUND: Cervical Cancer (CC), a leading cause of female mortality worldwide, demonstrates a direct association with high-risk human papillomavirus (HPV) infections. However, not all CC patients exhibit HPV infection, suggesting additional predisposing factors. Recently, disturbances in the oxidant-antioxidant balance have been implicated in CC development. This study explores the impact of gold nanoparticles (AuNPs) on the survival and antioxidant capacity of HeLa cells, aiming to contribute to novel CC therapy approaches. METHODS AND RESULTS: Synthesized and characterized AuNPs (25.5 nm, uniform distribution according to the DLS analysis) were administered to HeLa cells at varying concentrations. After 24 h, cell viability was assessed using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2 H-tetrazolium bromide) (MTT) assay. Real-time PCR measured expression levels of apoptosis-related genes (BCL2 associated X (BAX) and p53). Catalase and superoxide dismutase (SOD) activities, key antioxidant enzymes, were also evaluated post-AuNP treatment. AuNPs dose-dependently reduced HeLa cell viability, with an IC50 value of 113 µg/ml. BAX gene expression significantly increased, indicating pro-apoptotic effects. Moreover, enzyme activities significantly rose under AuNP influence. CONCLUSIONS: AuNPs demonstrated the potential to induce HeLa cell death by upregulating pro-apoptotic BAX gene expression and altering antioxidant system enzyme activities. These findings underscore the promise of AuNPs as a therapeutic avenue for CC, emphasizing their impact on crucial cellular processes involved in cancer progression.

Role of Oxidative Stress on the Etiology and Pathophysiology of Amyotrophic Lateral Sclerosis (ALS) and Its Relation with the Enteric Nervous System.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons in the spinal cord, cerebral cortex, and medulla oblongata. Most patients present a clinical phenotype of classic ALS-with predominant atrophy, muscle weakness, and fasciculations-and survival of 3 to 5 years following diagnosis. In the present review, we performed a literature search to provide an update on the etiology and pathophysiological mechanisms involved in ALS. There are two types of ALS: the familial form with genetic involvement, and the sporadic form with a multifactorial origin. ALS pathophysiology is characterized by involvement of multiple processes, including oxidative stress, glutamate excitotoxicity, and neuroinflammation. Moreover, it is proposed that conditioning risk factors affect ALS development, such as susceptibility to neurodegeneration in motor neurons, the intensity of performed physical activity, and intestinal dysbiosis with involvement of the enteric nervous system, which supports the existing theories of disease generation. To improve patients' prognosis and survival, it is necessary to further deepen our understanding of the etiopathogenesis of ALS.

The essential liaison of two copper proteins: the Cu-sensing transcription factor Mac1 and the Cu/Zn superoxide dismutase Sod1 in Saccharomyces cerevisiae.

Although copper is an essential trace element for cell function and viability, its excess can lead to protein oxidation, DNA cleavage, and ultimate cell damage. Cells have established a variety of regulatory mechanisms to ensure copper ion homeostasis. In Saccharomyces cerevisiae, copper sensing and response to copper deficiency are regulated by the transcription factor Mac1. Our group has previously reported that in addition to copper, several chromatin proteins modulate Mac1 functionality. In this study, based on a synthetic growth deficiency phenotype, we showed that the Cu/Zn superoxide dismutase Sod1 plays an important role in Mac1 transcriptional activity, in unchallenged nutrient-rich growth conditions. Sod1 is a multipotent cytoplasmic and mitochondrial enzyme, whose main known function is to detoxify the cell from superoxide ions. It has been previously reported that Sod1 also enters the nucleus and affects the transcription of several genes, some of which are involved in copper homeostasis under Cu-depleted (Wood and Thiele in J Biol Chem 284:404-413, 2009) or only under specific oxidative stress conditions (Dong et al. Mol Cell Biol 33:4041-4050, 2013; Tsang et al. Nar Commun 8:3446, 2014). We have shown that Sod1 physically interacts with Mac1 transcription factor and is important for the transactivation as well as its DNA-binding activities. On the other hand, a constitutively active mutant of Mac1 is not affected functionally by the Sod1 ablation, pointing out that Sod1 contributes to the maintenance of the copper-unchelated state of Mac1. In conclusion, we showed that Sod1-Mac1 interaction is vital for Mac1 functionality, regardless of copper medium deficiency, in unchallenged growth conditions, and we suggest that Sod1 enzymatic activity may modify the redox state of the cysteine-rich motifs in the Mac1 DNA-binding and transactivation domains.

The Interaction Effect of Sleep Deprivation and Treadmill Exercise in Various Durations on Spatial Memory with Respect to the Oxidative Status of Rats.

Sleep deprivation (SD) has deleterious effects on cognitive functions including learning and memory. However, some studies have shown that SD can improve cognitive functions. Interestingly, treadmill exercise has both impairment and improvement effects on memory function. In this study, we aimed to investigate the effect of SD for 4 (short-term) and 24 (long-term) hours, and two protocols of treadmill exercise (mild short-term and moderate long-term) on spatial memory performance, and oxidative and antioxidant markers in the serum of rats. Morris Water Maze apparatus was used to assess spatial memory performance. Also, SD was done using gentle handling method. In addition, the serum level of catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) was measured. The results showed that 24 h SD (but not 4 h) had negative effect on spatial memory performance, decreased SOD, CAT, and GSH-Px level, and increased MDA level. Long-term moderate (but not short-term mild) treadmill exercise had also negative effect on spatial memory performance, decreased SOD, CAT, and GSH-Px level, and increased MDA level. Interestingly, both protocols of treadmill exercise reversed spatial memory impairment and oxidative stress induced by 24 h SD. In conclusion, it seems that SD and treadmill exercise interact with each other, and moderate long-term exercise can reverse the negative effects of long-term SD on memory and oxidative status; although, it disrupted memory function and increased oxidative stress by itself.

The protective effect of arbutin against potassium bromate-induced oxidative damage in the rat brain.

This study aimed to investigate the protective effects of arbutin (ARB) against brain injury induced in rats with potassium bromate (KBrO3 ). The rats were divided into four groups as Group 1: Control (0.9% NaCl ml/kg/day p.), Group 2: KBrO3 (100 mg/kg (gavage), Group 3: ARB (50 mg/kg/day p.), and Group 4: KBrO3 + ARB (100 mg/kg (gavage) + 50 mg/kg/day p.). At the end of the fifth day of the study, the rats in all groups were killed, and their brain tissues were collected. In the collected brain tissues, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels were measured, and routine histopathological examinations were made. The MDA levels in the group that was exposed to KBrO3 were significantly higher than those in the control group (p ˂ 0.001). In comparison to the KBrO3 group, the MDA levels in the KBrO3 + ARB group were significantly lower (p ˂ 0.001). It was observed that SOD and CAT enzyme activity levels were significantly lower in the KBrO3 group compared to the control group (p ˂ 0.001), while these levels were significantly higher in the KBrO3 + ARB group than in the KBrO3 group (p ˂ 0.001). Additionally, the group that was subjected to KBrO3 toxicity, as well as ARB administration, had much lower levels of histopathologic signs than the group that was subjected to KBrO3 toxicity only. Consequently, it was found that KBrO3 exposure led to injury in the brain tissues of the rats, and using ARB was effective in preventing this injury.

Inhibition of Enzymes Involved in Neurodegenerative Disorders and Aß1-40 Aggregation by Citrus limon Peel Polyphenol Extract.

Alzheimer's (AD) and Parkinson's diseases (PD) are multifactorial neurogenerative disorders of the Central Nervous System causing severe cognitive and motor deficits in elderly people. Because treatment of AD and PD by synthetic drugs alleviates the symptoms often inducing side effects, many studies have aimed to find neuroprotective properties of diet polyphenols, compounds known to act on different cell signaling pathways. In this article, we analyzed the effect of polyphenols obtained from the agro-food industry waste of Citrus limon peel (LPE) on key enzymes of cholinergic and aminergic neurotransmission, such as butyryl cholinesterase (BuChE) and monoamine oxidases (MAO)-A/B, on Aß1-40 aggregation and on superoxide dismutase (SOD) 1/2 that affect oxidative stress. In our in vitro assays, LPE acts as an enzyme inhibitor on BuChE (IC50 ~ 73 µM), MAO-A/B (IC50 ~ 80 µM), SOD 1/2 (IC50 ~ 10-20 µM) and interferes with Aß1-40 peptide aggregation (IC50 ~ 170 µM). These results demonstrate that LPE behaves as a multitargeting agent against key factors of AD and PD by inhibiting to various extents BuChE, MAOs, and SODs and reducing Aß-fibril aggregation. Therefore, LPE is a promising candidate for the prevention and management of AD and PD symptoms in combination with pharmacological therapies.

Anti-SOD1 Nanobodies That Stabilize Misfolded SOD1 Proteins Also Promote Neurite Outgrowth in Mutant SOD1 Human Neurons.

ALS-linked mutations induce aberrant conformations within the SOD1 protein that are thought to underlie the pathogenic mechanism of SOD1-mediated ALS. Although clinical trials are underway for gene silencing of SOD1, these approaches reduce both wild-type and mutated forms of SOD1. Here, we sought to develop anti-SOD1 nanobodies with selectivity for mutant and misfolded forms of human SOD1 over wild-type SOD1. Characterization of two anti-SOD1 nanobodies revealed that these biologics stabilize mutant SOD1 in vitro. Further, SOD1 expression levels were enhanced and the physiological subcellular localization of mutant SOD1 was restored upon co-expression of anti-SOD1 nanobodies in immortalized cells. In human motor neurons harboring the SOD1 A4V mutation, anti-SOD1 nanobody expression promoted neurite outgrowth, demonstrating a protective effect of anti-SOD1 nanobodies in otherwise unhealthy cells. In vitro assays revealed that an anti-SOD1 nanobody exhibited selectivity for human mutant SOD1 over endogenous murine SOD1, thus supporting the preclinical utility of anti-SOD1 nanobodies for testing in animal models of ALS. In sum, the anti-SOD1 nanobodies developed and presented herein represent viable biologics for further preclinical testing in human and mouse models of ALS.

3',4'-Dihydroxyflavonol (DiOHF) prevents DNA damage, lipid peroxidation and inflammation in ovarian ischaemia-reperfusion injury of rats.

This study aimed to determine the effect of 3',4'-Dihydroxyflavonol (DiOHF) on lipid peroxidation, DNA damage and inflammation in ovarian ischaemia (I)-reperfusion (R) injury. This study was performed on 44 Wistar-albino female rats. Groups were designed as Control; Sham; I/R (the left ovary was ligated for 2 h and then reperfused for 2 h); I/R + DiOHF (after 2 h ischaemia and 2 h reperfusion, 30 mg/kg of DiOHF was given intraperitoneally and reperfusion was allowed for 2 h more); I + DiOHF + R (after 2 h I, 30 mg/kg of DiOHF was given at the beginning of 2 h reperfusion); DiOHF + I/R (2 h after DiOHF administration, the left ovary was ligated for 2 h and then reperfused for 2 h). Blood and ovarian tissue samples were analysed for GSH, MDA, 8-OHdG, SOD, and IL-6. Ovarian tissue was examined histopathologically. Ovarian I/R has led to inflammation and oxidative damage. However, DiOHF activated the antioxidant system and prevented DNA damage induced by I/R in ovarian tissue. Vascularisation, oedema, and inflammation also occurred in ovarian tissue in I/R group. The results of this study indicated that I/R led to disturbance of the oxidant/antioxidant system balance and increased DNA damage; however, DiOHF supplementation prevented DNA damage, lipid peroxidation and inflammation by increasing the antioxidant system in ovarian I/R injury in rats. However, in potential I/R situations, DiOHF application appears to be beneficial in reducing inflammation, oxidant injury, and DNA damage, and in activating the antioxidant system. IMPACT STATEMENTWhat is already known on this subject? Ischaemia/reperfusion (I/R) injuries lead to damage in cells or tissues due to insufficient blood flow.What do the results of this study add? Increased DNA injury and inflammatory response (IL-6) and structural impairment were treated by administration of intraperitoneal (DiOHF) which strongly stimulated the antioxidant system, inhibited antioxidant activities, prevented DNA damage and inflammation process.What are the implications of these findings for clinical practice and/or further research? This study's strength is that it is the first research demonstrates the prevention of DNA damage in ovarian I/R by DiOHF supplementation. This flavonoid (DiOHF) may be used for treatment in different ovarian ischaemia/reperfusion.

Histomorphological and Biochemical Analysis of Rat Model of Menopausal Skin Aging.

The study examined the skin histomorphology and biochemistry in mature ovariectomized rats treated and not treated with estrogen. Biochemical parameters (superoxide dismutase, malondialdehyde, and hydroxyproline content) were measured in dorsal skin samples collected in 50 days after surgery. The morphology of dorsal skin was analyzed under a microscope. In ovariectomized rats, the skin levels of superoxide dismutase and hydroxyproline were significantly lower, while the superoxide dismutase content was significantly higher than in shamoperated animals (p<0.05). Estrogen therapy significantly increased the levels of superoxide dismutase and hydroxyproline and reduced superoxide dismutase level in ovariectomized rats in comparison with the corresponding parameters in untreated ovariectomized animals (p<0.05). Histomorphological analysis of the skin from non-treated ovariectomized rats revealed reduced vascularization and lower density of papillary capillaries in comparison with these parameters in sham-operated controls; estrogen treatment prevented these changes. We concluded that ovariectomized rats can be employed as a model of aging skin in menopause.

Copper-only superoxide dismutase enzymes and iron starvation stress in Candida fungal pathogens.

Copper (Cu)-only superoxide dismutases (SOD) represent a newly characterized class of extracellular SODs important for virulence of several fungal pathogens. Previous studies of the Cu-only enzyme SOD5 from the opportunistic fungal pathogen Candida albicans have revealed that the active-site structure and Cu binding of SOD5 strongly deviate from those of Cu/Zn-SODs in its animal hosts, making Cu-only SODs a possible target for future antifungal drug design. C. albicans also expresses a Cu-only SOD4 that is highly similar in sequence to SOD5, but is poorly characterized. Here, we compared the biochemical, biophysical, and cell biological properties of C. albicans SOD4 and SOD5. Analyzing the recombinant proteins, we found that, similar to SOD5, Cu-only SOD4 can react with superoxide at rates approaching diffusion limits. Both SODs were monomeric and they exhibited similar binding affinities for their Cu cofactor. In C. albicans cultures, SOD4 and SOD5 were predominantly cell wall proteins. Despite these similarities, the SOD4 and SOD5 genes strongly differed in transcriptional regulation. SOD5 was predominantly induced during hyphal morphogenesis, together with a fungal burst in reactive oxygen species. Conversely, SOD4 expression was specifically up-regulated by iron (Fe) starvation and controlled by the Fe-responsive transcription factor SEF1. Interestingly, Candida tropicalis and the emerging fungal pathogen Candida auris contain a single SOD5-like SOD rather than a pair, and in both fungi, this SOD was induced by Fe starvation. This unexpected link between Fe homeostasis and extracellular Cu-SODs may help many fungi adapt to Fe-limited conditions of their hosts.

TNF receptor-associated factor 6 interacts with ALS-linked misfolded superoxide dismutase 1 and promotes aggregation.

Amyotrophic lateral sclerosis (ALS) is a fatal disease, characterized by the selective loss of motor neurons leading to paralysis. Mutations in the gene encoding superoxide dismutase 1 (SOD1) are the second most common cause of familial ALS, and considerable evidence suggests that these mutations result in an increase in toxicity due to protein misfolding. We previously demonstrated in the SOD1G93A rat model that misfolded SOD1 exists as distinct conformers and forms deposits on mitochondrial subpopulations. Here, using SOD1G93A rats and conformation-restricted antibodies specific for misfolded SOD1 (B8H10 and AMF7-63), we identified the interactomes of the mitochondrial pools of misfolded SOD1. This strategy identified binding proteins that uniquely interacted with either AMF7-63 or B8H10-reactive SOD1 conformers as well as a high proportion of interactors common to both conformers. Of this latter set, we identified the E3 ubiquitin ligase TNF receptor-associated factor 6 (TRAF6) as a SOD1 interactor, and we determined that exposure of the SOD1 functional loops facilitates this interaction. Of note, this conformational change was not universally fulfilled by all SOD1 variants and differentiated TRAF6 interacting from TRAF6 noninteracting SOD1 variants. Functionally, TRAF6 stimulated polyubiquitination and aggregation of the interacting SOD1 variants. TRAF6 E3 ubiquitin ligase activity was required for the former but was dispensable for the latter, indicating that TRAF6-mediated polyubiquitination and aggregation of the SOD1 variants are independent events. We propose that the interaction between misfolded SOD1 and TRAF6 may be relevant to the etiology of ALS.

Functional diversity between HSP70 paralogs caused by variable interactions with specific co-chaperones.

Heat shock protein 70 (HSP70) chaperones play a central role in protein quality control and are crucial for many cellular processes, including protein folding, degradation, and disaggregation. Human HSP70s compose a family of 13 members that carry out their functions with the aid of even larger families of co-chaperones. A delicate interplay between HSP70s and co-chaperone recruitment is thought to determine substrate fate, yet it has been generally assumed that all Hsp70 paralogs have similar activities and are largely functionally redundant. However, here we found that when expressed in human cells, two highly homologous HSP70s, HSPA1A and HSPA1L, have opposing effects on cellular handling of various substrates. For example, HSPA1A reduced aggregation of the amyotrophic lateral sclerosis-associated protein variant superoxide dismutase 1 (SOD1)-A4V, whereas HSPA1L enhanced its aggregation. Intriguingly, variations in the substrate-binding domain of these HSP70s did not play a role in this difference. Instead, we observed that substrate fate is determined by differential interactions of the HSP70s with co-chaperones. Whereas most co-chaperones bound equally well to these two HSP70s, Hsp70/Hsp90-organizing protein (HOP) preferentially bound to HSPA1L, and the Hsp110 nucleotide-exchange factor HSPH2 preferred HSPA1A. The role of HSPH2 was especially crucial for the HSPA1A-mediated reduction in SOD1-A4V aggregation. These findings reveal a remarkable functional diversity at the level of the cellular HSP70s and indicate that this diversity is defined by their affinities for specific co-chaperones such as HSPH2.

Cathepsin A contributes to left ventricular remodeling by degrading extracellular superoxide dismutase in mice.

In the heart, the serine carboxypeptidase cathepsin A (CatA) is distributed between lysosomes and the extracellular matrix (ECM). CatA-mediated degradation of extracellular peptides may contribute to ECM remodeling and left ventricular (LV) dysfunction. Here, we aimed to evaluate the effects of CatA overexpression on LV remodeling. A proteomic analysis of the secretome of adult mouse cardiac fibroblasts upon digestion by CatA identified the extracellular antioxidant enzyme superoxide dismutase (EC-SOD) as a novel substrate of CatA, which decreased EC-SOD abundance 5-fold. In vitro, both cardiomyocytes and cardiac fibroblasts expressed and secreted CatA protein, and only cardiac fibroblasts expressed and secreted EC-SOD protein. Cardiomyocyte-specific CatA overexpression and increased CatA activity in the LV of transgenic mice (CatA-TG) reduced EC-SOD protein levels by 43%. Loss of EC-SOD-mediated antioxidative activity resulted in significant accumulation of superoxide radicals (WT, 4.54 µmol/mg tissue/min; CatA-TG, 8.62 µmol/mg tissue/min), increased inflammation, myocyte hypertrophy (WT, 19.8 µm; CatA-TG, 21.9 µm), cellular apoptosis, and elevated mRNA expression of hypertrophy-related and profibrotic marker genes, without affecting intracellular detoxifying proteins. In CatA-TG mice, LV interstitial fibrosis formation was enhanced by 19%, and the type I/type III collagen ratio was shifted toward higher abundance of collagen I fibers. Cardiac remodeling in CatA-TG was accompanied by an increased LV weight/body weight ratio and LV end diastolic volume (WT, 50.8 µl; CatA-TG, 61.9 µl). In conclusion, CatA-mediated EC-SOD reduction in the heart contributes to increased oxidative stress, myocyte hypertrophy, ECM remodeling, and inflammation, implicating CatA as a potential therapeutic target to prevent ventricular remodeling.

Differential sensitivities of triple-negative breast cancer stem cell towards various doses of vitamin C: An insight into the internal antioxidant systems.

Cancer stem cells (CSCs) are quiescent and self-renewing, having low levels of reactive oxygen species (ROS), and are responsible for cancer recurrence after chemotherapy and radiotherapy. However, the interplay between the ROS production and scavenging from the oxidative stress has never been studied in breast CSCs. In this present study, we have investigated the cellular energetics of two triple-negative breast cancer stem cells (MDA-MB-231 and MDA-MB-468) treated with two pharmacological doses of vitamin C (10 and 20 mM) that generated ROS. Our results indicate a differential behavior of ROS scavenging by both the CSCs. MDA-MB-468 CSCs exhibited higher resistance to ROS induced damage owing to the higher antioxidant activity, lower mitochondrial damage, and less decrease in membrane potential (ΔΨm ) as compared with MDA-MB-231 CSCs. Moreover, MDA-MB-231 CSCs exhibited an intrinsic apoptosis pathway by activating the cytochrome c, caspase-9, 3, 7, and cleaved PARP upon treatment with vitamin C. This data suggests a possible strategy for targeting breast CSCs using vitamin C. Taken together, the CSCs from MDA-MB-231 could be easily targeted by high/pharmacological doses of vitamin C (≥20 mM) thereby indicating a less robust internal antioxidant machinery.

Effect of APTES modified TiO2 on antioxidant enzymes activity secreted by Escherichia coli and Staphylococcus epidermidis.

In this work, the impact of APTES-modified TiO2 photocatalysts on antioxidant enzymes (catalase and superoxide dismutase) activity secreted by bacteria was presented. Microbial tests has been examined using Escherichia coli (ATCC 29425) and Staphylococcus epidermidis (ATCC 49461) as model organisms. It was found that APTES-TiO2 affected the activity of antioxidant enzymes. Additionally, obtained APTES-TiO2 photocatalysts were capable of total E. coli and S. epidermidis inactivation under artificial solar light irradiation. The sample modified with the concentration of APTES equals 300 mM (TiO2-4h-120°C-300mM) showed the strongest photocatalytic activity toward both bacteria species. The two-stage photocatalytic mechanism of bacteria response to photocatalysts was proposed.

The effect of Crocin on TFAM and PGC-1α expression and Catalase and Superoxide dismutase activities following cholestasis-induced neuroinflammation in the striatum of male Wistar rats.

Bile secretion is a physiological function that is disrupted following Bile Duct Ligation (BDL) and induces cholestasis. Cholestasis is a bile flow reduction that induces apoptosis, oxidative stress, and inflammation, and alters the expression of genes. Evidence shows the relationship between cholestasis and neuroinflammation. Cholestasis via attenuating mitochondrial biogenesis and anti-oxidant activity can induce neuroinflammation and apoptosis. Mitochondrial transcriptional factor A (TFAM) and Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) are involved in mitochondrial biogenesis, and TFAM, PGC-1α, Catalase (CAT), and Superoxide dismutase (SOD) have a role in upregulating antioxidant pathways. On the other hand, many studies have shown the neuroprotective effects of Crocin, the water-soluble carotenoid of Saffron (Crocus sativus L.). In this study, we aimed to investigate the effect of Crocin on the level of TFAM, PGC-1α, CAT, and SOD following cholestasis-induced neuroinflammation in the rat's striatum. Cholestasis was induced by BDL surgery and administration of Crocin was intraperitoneal, at the dose of 30 mg/kg every day, 24 h after BDL surgery up to thirty days. The results showed that TFAM, PGC-1α, and SOD were decreased following cholestasis; while, CAT was increased. In addition, Crocin restored the effects of cholestasis on the level of TFAM, PGC-1α, and SOD. In conclusion, Crocin may have improvement effects on cholestasis-induced neuroinflammation in the rat's striatum.