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1.
Chemosphere ; 286(Pt 1): 131625, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34303901

RESUMEN

Captan is a non-systematic fungicide widely used in agricultural production, and its residues have been found in the environment and daily diet. Previous studies confirmed that captan exerts several toxic effects on tissues, but its effect on the mammalian female reproductive system is unclear. In current study, we reported that captan affected mouse ovarian homeostasis and disrupted female hormone receptor expression, leading to impaired follicular development. Ovarian follicles from the captan exposure group showed an increased level of inflammation, endoplasmic reticulum stress and apoptosis. In addition, captan exposure disrupted oocyte development. Transcriptomic analysis indicated that captan changed multiple genes expression in oocytes, including autophagy and apoptosis. Further molecular testing showed that captan induced oxidative stress and mitochondrial dysfunction, as indicated by the increased level of reactive oxygen species, disrupted mitochondrial structure and distribution, and depolarized membrane potential. Furthermore, captan triggered DNA damage, autophagy and early apoptosis, as shown by the enhanced levels of γ-H2AX, LC3, and Annexin-V and increased expression of related genes. Taken together, these results indicated that captan exposure impairs ovarian homeostasis and subsequently affects oocyte development.


Asunto(s)
Captano , Oocitos , Animales , Apoptosis , Captano/metabolismo , Femenino , Homeostasis , Ratones , Mitocondrias/metabolismo , Oocitos/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo
2.
Theriogenology ; 178: 85-94, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-34808561

RESUMEN

Heat stress causes oxidative damage and induces excessive cell apoptosis and thus affects the development and/or even causes the death of preimplantation embryos. The effects of baicalin on the developmental competence of heat-stressed mouse embryos were investigated in this experiment. Two-cell embryos were cultured in the presence of baicalin and subjected to heat stress (42 °C for 1 h) at their blastocyst stage followed by continuous culture at 37 °C until examination. The results showed that heat stress (H group) increased reactive oxygen species (ROS) production, apoptosis and even embryo death, along with reductions in both mitochondrial activity and membrane potential (ΔΨm). Both heat stress (H group) and inhibition of the ERK1/2 signaling pathway (U group) led to significantly reduced expression levels of the genes c-fos, AP-1 and ERK2, and the phosphorylation of ERK1/2 and c-Fos, along with significantly increased c-Jun mRNA expression and phosphorylation levels. These negative effects of heat stress on the ERK1/2 signaling pathway were neutralized by baicalin treatment. To explore the signal transduction mechanism of baicalin in improving embryonic tolerance to heat stress, mitochondrial quality and apoptosis rate in the mouse blastocysts were also examined. Baicalin was found to up-regulate the expression of mtDNA and TFAM mRNA, increased mitochondria activity and ΔΨm, and improved the cellular mitochondria quality of mouse blastocysts undergoing heat stress. Moreover, baicalin decreased Bax transcript abundance in blastocyst, along with an increase in the blastocyst hatching rate, which were negatively affected by heat stress. Our findings suggest that baicalin improves the developmental capacity and quality of heat-stressed mouse embryos via a mechanism whereby mitochondrial quality is improved by activating the ERK1/2 signaling pathway and inducing anti-cellular apoptosis.


Asunto(s)
Técnicas de Cultivo de Embriones , Termotolerancia , Animales , Apoptosis , Blastocisto/metabolismo , Técnicas de Cultivo de Embriones/veterinaria , Desarrollo Embrionario , Flavonoides , Sistema de Señalización de MAP Quinasas , Ratones , Mitocondrias/metabolismo , Transducción de Señal
3.
Free Radic Biol Med ; 178: 369-379, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34906725

RESUMEN

Mitochondria participate in essential cellular functions, including energy production, metabolism, redox homeostasis regulation, intracellular Ca2+ handling, apoptosis, and cell fate determination. Disruption of mitochondrial homeostasis under pathological conditions results in mitochondrial reactive oxygen species (ROS) generation and energy insufficiency, which further disturb mitochondrial and cellular homeostasis in a deleterious loop. Mitochondrial redox status has therefore become a potential target for therapy against cardiovascular diseases. In this review, we highlight recent progress in determining the roles of mitochondrial processes in regulating mitochondrial redox status, including mitochondrial dynamics (fusion-fission pathways), mitochondrial cristae remodeling, mitophagy, biogenesis, and mitochondrion-organelle interactions (endoplasmic reticulum-mitochondrion interactions, nucleus-mitochondrion communication, and lipid droplet-mitochondrion interactions). The strategies that activate vagal system include direct vagal activation (electrical vagal stimulation and administration of vagal neurotransmitter acetylcholine) and pharmacological modulation (choline and cholinesterase inhibitors). The vagal system plays an important role in maintaining mitochondrial homeostasis and suppressing mitochondrial oxidative stress by promoting mitochondrial biogenesis and mitophagy, moderating mitochondrial fusion and fission, strengthening mitochondrial cristae stabilization, regulating mitochondrion-organelle interactions, and inhibiting mitochondrial Ca2+ overload. Therefore, enhancement of vagal activity can maintain mitochondrial homeostasis and represents a promising therapeutic strategy for cardiovascular diseases.


Asunto(s)
Enfermedades Cardiovasculares , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/metabolismo , Homeostasis , Humanos , Mitocondrias/metabolismo , Dinámicas Mitocondriales , Oxidación-Reducción
4.
Food Chem ; 367: 130767, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-34391996

RESUMEN

This study aimed to investigate the effect of caspase-3 inhibitor in mitochondrial apoptosis activation on structure protein degradation during postmortem storage. Mitochondrial dysfunction, apoptotic factors, structure protein degradation and the myofibrillar rupture index between the control and caspase-3 inhibitor groups were determined. The results show caspase-3 inhibitor repressed the mitochondrial membrane permeability and mitochondrial swelling, as well as increased mitochondrial membrane potential, causing a decrease in the release of cytochrome c from mitochondria to cytoplasm and caspase-9/3 activities (P < 0.05). Subsequently, small myofibrillar proteins (desmin and troponin-T) were susceptible to degradation, initiating texture deterioration. By contrast, giant structure proteins (titin and nebulin) were degraded during later postmortem storage, predominantly contributing to fish softening. The results further suggest that caspase-3 is involved in degradation of structure proteins during postmortem through mitochondrial apoptosis pathways.


Asunto(s)
Esocidae , Mitocondrias , Animales , Apoptosis , Caspasa 3/genética , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Esocidae/metabolismo , Mitocondrias/metabolismo , Membranas Mitocondriales/metabolismo
5.
Gene ; 806: 145929, 2022 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-34461150

RESUMEN

The body color of Neocaridina denticulate sinensis is a compelling phenotypic trait, in which a cascade of carotenoid metabolic processes plays an important role. The study was conducted to compare the transcriptome of cephalothoraxes among three pigmentation phenotypes (red, blue, and chocolate) of N. denticulate sinensis. The purpose of this study was to explore the candidate genes associated with different colors of N. denticulate sinensis. Nine cDNA libraries in three groups were constructed from the cephalothoraxes of shrimps. After assembly, 75022 unigenes were obtained in total with an average length of 1026 bp and N50 length of 1876 bp. There were 45977, 25284, 23605, 21913 unigenes annotated in the Nr, Swissprot, KOG, and KEGG databases, respectively. Differential expression analysis revealed that there were 829, 554, and 3194 differentially expressed genes (DEGs) in RD vs BL, RD vs CH, and BL vs CH, respectively. These DEGs may play roles in the absorption, transport, and metabolism of carotenoids. We also emphasized that electron transfer across the inner mitochondrial membrane (IMM) was a key process in pigment metabolism. In addition, a total of 6328 simple sequence repeats (SSRs) were also detected in N. denticulate sinensis. The results laid a solid foundation for further research on the molecular mechanism of integument pigmentation in the crustacean and contributed to developing more attractive aquatic animals.


Asunto(s)
Proteínas de Artrópodos/genética , Carotenoides/metabolismo , Decápodos/genética , Pigmentación/genética , Transcriptoma , Animales , Organismos Acuáticos , Proteínas de Artrópodos/clasificación , Proteínas de Artrópodos/metabolismo , Transporte Biológico , Color , Bases de Datos Genéticas , Decápodos/anatomía & histología , Decápodos/metabolismo , Agua Dulce , Regulación de la Expresión Génica , Biblioteca de Genes , Ontología de Genes , Repeticiones de Microsatélite , Mitocondrias/metabolismo , Membranas Mitocondriales/metabolismo , Anotación de Secuencia Molecular , Carácter Cuantitativo Heredable
6.
Biol Trace Elem Res ; 200(1): 261-270, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33566285

RESUMEN

Mitochondria are vital cellular organelles associated with energy production as well as cell signaling pathways. These organelles, responsible for metabolism, are highly abundant in hepatocytes that make them key players in hepatotoxicity. The literature suggests that mitochondria are targeted by various environmental pollutants. Arsenic, a toxic metalloid known as an environmental pollutant, readily contaminates drinking water and exerts toxic effects. It is toxic to various cellular organs; among them, the liver seems to be most affected. A growing body of evidence suggests that within cells, arsenic is highly toxic to mitochondria and reported to cause oxidative stress and alter an array of signaling pathways and functions. Hence, it is imperative to highlight the mechanisms associated with altered mitochondrial functions and integrity in arsenic-induced liver toxicity. This review provides the details of mechanistic aspects of mitochondrial dysfunction in arsenic-induced hepatotoxicity as well as various ameliorative measures undertaken concerning mitochondrial functions.


Asunto(s)
Intoxicación por Arsénico , Arsénico , Arsénico/metabolismo , Arsénico/toxicidad , Intoxicación por Arsénico/metabolismo , Humanos , Hígado/metabolismo , Mitocondrias/metabolismo , Estrés Oxidativo
7.
Biochim Biophys Acta Gen Subj ; 1866(1): 130017, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34624450

RESUMEN

BACKGROUND: Autophagy, a highly conserved homeostatic mechanism, is essential for cell survival. The decline of autophagy function has been implicated in various diseases as well as aging. Although mitochondria play a key role in the autophagy process, whether mitochondrial-derived peptides are involved in this process has not been explored. METHODS: We developed a high through put screening method to identify potential autophagy inducers among mitochondrial-derived peptides. We used three different cell lines, mice, c.elegans, and a human cohort to validate the observation. RESULTS: Humanin, a mitochondrial-derived peptide, increases autophagy and maintains autophagy flux in several cell types. Humanin administration increases the expression of autophagy-related genes and lowers accumulation of harmful misfolded proteins in mice skeletal muscle, suggesting that humanin-induced autophagy potentially contributes to the improved skeletal function. Moreover, autophagy is a critical role in humanin-induced lifespan extension in C. elegans. CONCLUSIONS: Humanin is an autophagy inducer. GENERAL SIGNIFICANCE: This paper presents a significant, novel discovery regarding the role of the mitochondrial derived peptide humanin in autophagy regulation and as a possible therapeutic target for autophagy in various age-related diseases.


Asunto(s)
Autofagia/fisiología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Músculo Esquelético/metabolismo , Envejecimiento , Animales , Caenorhabditis elegans/metabolismo , Línea Celular , Supervivencia Celular , Células HEK293 , Homeostasis , Humanos , Péptidos y Proteínas de Señalización Intracelular/fisiología , Longevidad , Masculino , Ratones , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Músculo Esquelético/fisiología , Péptidos/metabolismo
8.
Biochim Biophys Acta Gen Subj ; 1866(1): 130043, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34710487

RESUMEN

BACKGROUND: Paraoxonase 2 (PON2) a known anti-apoptotic protein, has not been explored against Nε-(carboxymethyl)lysine (CML), induced mitochondrial dysfunction and apoptosis in human retinal cells. Hence this present study aims to investigate the potential role of PON2 in mitigating CML-induced mitochondrial dysfunction in these cells. METHODS: PON2 protein was quantified in HRECs (Human retinal endothelial cells), ARPE-19 (Retinal pigment epithelial cells) cells upon CML treatment and also in cadaveric diabetic retina vs respective controls. ROS production, mitochondrial membrane potential (MMP), mitochondrial permeability transition pore (mPTP) opening, the release of Cyt-c, Bax, Caspase-3, Fis1, Mfn1, Mfn2, mitochondrial morphology, and the signaling pathway was assessed using DCFDA, JC-1, CoCl2, immunofluorescence or western blotting analysis in both loss-of-function or gain-of-function experiments. RESULTS: PON2 protein was downregulated in HREC and ARPE-19 cells upon CML treatment as well as in the diabetic retina (p = 0.035). Decrease in PON2 augments Fis1 expression resulting in fragmentation of mitochondria and enhances the ROS production, decreases MMP, facilitates mPTP opening, and induces the release of Cyt-c, which activates the pro-apoptotic pathway. Whereas PON2 overexpression similar to SP600125 (a specific JNK inhibitor) was able to decrease Fis1 (p = 0.036) and reverse the Bcl-2 and Bax ratio, and inhibit the JNK1/2 signaling pathway. CONCLUSION: Our results confirm that PON2 has an anti-apoptotic role against the CML mediated mitochondrial dysfunction and inhibits apoptosis through the JNK-Fis1 axis. GENERAL SIGNIFICANCE: We hypothesis that enhancing PON2 may provide a better therapeutic potential against diabetic vascular disease.


Asunto(s)
Arildialquilfosfatasa/metabolismo , Mitocondrias/metabolismo , Retina/metabolismo , Apoptosis/fisiología , Arildialquilfosfatasa/fisiología , Caspasa 3/metabolismo , Citocromos c/metabolismo , Células Endoteliales/metabolismo , Humanos , Sistema de Señalización de MAP Quinasas/fisiología , Potencial de la Membrana Mitocondrial/fisiología , Sustancias Protectoras , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Retina/fisiología , Transducción de Señal/fisiología
9.
Methods Mol Biol ; 2363: 183-197, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34545494

RESUMEN

Mitochondria are subcellular organelles with their own genome and expression system, including translation machinery to make proteins. Several independent studies have shown that translation is an essential regulatory step in expression of the plant mitochondrial genome. Thus, the study of mitochondrial translation seems to be crucial for the comprehension of plant mitochondrial biogenesis and maintenance. In organello protein synthesis in isolated mitochondria is a direct method to visualize the translational products of this organellar genetic system. In this method, highly purified, functional mitochondria synthesize proteins in the presence of radiolabeled amino acids, such as methionine, and an energy regeneration system. The labeled, newly synthesized polypeptides are separated by SDS-polyacrylamide gel electrophoresis and are detected by autoradiography. Here we describe the detailed protocol for in organello labeling of translation products that was optimized for mitochondria isolated from rosette leaves and liquid culture seedlings of Arabidopsis thaliana plants.


Asunto(s)
Arabidopsis , Arabidopsis/genética , Mitocondrias/metabolismo , Proteínas Mitocondriales , Hojas de la Planta/metabolismo , Biosíntesis de Proteínas , Plantones
10.
Methods Mol Biol ; 2363: 199-213, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34545495

RESUMEN

Mitochondria actively participate in oxygenic metabolism and are one of the major sources of reactive oxygen species (ROS) production in plant cells. However, instead of measuring ROS concentrations in organelles it is more worthwhile to observe active ROS generation or downstream oxidation products, because the steady state level of ROS is easily buffered. Here, we describe how to measure the in vitro production of superoxide anion radicals (O2·-) by mitochondria and the release of O2·- into the cytosol. A method to determine glutathione, which is the most abundant mitochondrial low-mass antioxidant, is presented since changes in the redox state of glutathione can be indicative of the oxidative action of ROS. The identification of oxidative damage to mitochondrial components is the ultimate symptom that ROS homeostasis is not under control. We present how to determine the extent of oxidation of membrane lipids and the carbonylation of mitochondrial proteins. In summary, oxidative stress symptoms have to be analyzed at different levels, including ROS production, scavenging capacity, and signs of destruction, which only together can be considered markers of mitochondrial ROS status.


Asunto(s)
Mitocondrias , Estrés Oxidativo , Glutatión/metabolismo , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Oxidación-Reducción , Especies Reactivas de Oxígeno/metabolismo
11.
Methods Mol Biol ; 2363: 215-234, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34545496

RESUMEN

Mitochondria are central hubs of redox biochemistry in the cell. An important role of mitochondrial carbon metabolism is to oxidize respiratory substrates and to pass the electrons down the mitochondrial electron transport chain to reduce oxygen and to drive oxidative phosphorylation. During respiration, reactive oxygen species are produced as a side reaction, some of which in turn oxidize cysteine thiols in proteins. Hence, the redox status of cysteine-containing mitochondrial proteins has to be controlled by the mitochondrial glutathione and thioredoxin systems, which draw electrons from metabolically derived NADPH. The redox status of mitochondrial cysteines can undergo fast transitions depending on the metabolic status of the cell, as for instance at early seed germination. Here, we describe a state-of-the-art method to quantify redox state of protein cysteines in isolated Arabidopsis seedling mitochondria of controlled metabolic and respiratory state by MS2-based redox proteomics using the isobaric thiol labeling reagent Iodoacetyl Tandem Mass Tag™ (iodoTMT). The procedure is also applicable to isolated mitochondria of other plant and nonplant systems.


Asunto(s)
Arabidopsis , Arabidopsis/metabolismo , Cisteína/metabolismo , Espectrometría de Masas , Mitocondrias/metabolismo , Oxidación-Reducción , Proteoma/metabolismo
12.
Methods Mol Biol ; 2363: 263-278, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34545498

RESUMEN

C-to-U RNA editing in mitochondria and plastids is widespread in almost all terrestrial plants, where it mainly changes codons to encode conserved amino acids in organelle mRNAs. In flowering plants, the number of RNA editing sites reaches 400-600 in mitochondria and about 40 in plastids, respectively. To date, more than 100 factors involved in RNA editing have been identified. Since target cytidines of each factor are often distributed across multiple transcripts, comprehensive monitoring of all RNA editing sites is necessary for their characterization. Comparing the signals of C and T in the Sanger sequencing chromatogram of RT-PCR products is the most frequently employed method for quantification of RNA editing efficiency, although several methods based on next-generation sequencing have been developed. I here describe a quick and easy method for quantification of RNA editing efficiency at several hundred sites using the Sanger sequencing chromatogram data.


Asunto(s)
Edición de ARN , Mitocondrias/genética , Mitocondrias/metabolismo , Plastidios/metabolismo , ARN/metabolismo , ARN Mensajero/metabolismo , ARN Mitocondrial/genética , ARN de Planta/genética , ARN de Planta/metabolismo
13.
Methods Mol Biol ; 2363: 279-300, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34545499

RESUMEN

Knowledge of mitochondrial transcription start sites and promoter sequences is key to understanding mechanisms of transcription initiation in plant mitochondria. Transcription start sites can be straightforwardly determined by the mapping of primary transcript 5' ends. This chapter describes a next-generation sequencing-based protocol for the mitochondrial genome-wide mapping of transcription start sites in Arabidopsis thaliana. Like other strategies aiming at the determination of primary transcript 5' ends, this protocol exploits that only primary but not processed transcripts are 5'-triphosphorylated and, based on this property, can be enzymatically selected for. However, it uses nascent transcripts, in order to (1) enhance mitochondrial coverage compared with other compartments, (2) reduce rRNA and other background, and (3) also capture the primary 5' ends of rapidly degraded or processed transcripts.


Asunto(s)
Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Mitocondrias/genética , Mitocondrias/metabolismo , Regiones Promotoras Genéticas , Sitio de Iniciación de la Transcripción , Transcripción Genética
14.
Methods Mol Biol ; 2363: 321-334, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34545501

RESUMEN

Nuclear, mitochondrial and plastidic DNA is constantly exposed to conditions, such as ultraviolet radiation or reactive oxygen species, which will induce chemical modifications to the nucleotides. Unless repaired, these modifications can lead to mutations, so the nucleus, mitochondria and plastids each contains a number of DNA repair systems. We here describe assays for measuring the enzyme activities associated with the base-excision repair pathway in potato tuber mitochondria. As the name implies, this pathway involves removing a modified base and replacing it with an undamaged base. Activity of each of the enzymes involved, DNA glycosylase, apurinic/apyrimidinic endonuclease, DNA polymerase and DNA ligase can be measured by incubating a mitochondrial extract with a specifically designed oligonucleotide. After incubation, the reaction mixture is separated on a polyacrylamide gel, and the amounts of specific products formed is estimated by autoradiography, which makes it possible to calculate the enzymatic activity.


Asunto(s)
Reparación del ADN , Mitocondrias , ADN Glicosilasas/genética , ADN Glicosilasas/metabolismo , Enzimas Reparadoras del ADN/genética , ADN Mitocondrial , ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , Mitocondrias/genética , Mitocondrias/metabolismo , Rayos Ultravioleta
15.
Gene ; 809: 146012, 2022 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-34655719

RESUMEN

Cancer cells rewire metabolic pathways as they demand more ATP and building blocks for proliferation. Glucose is the most consumed nutrient by cancer cells and metabolized to lactate even in the presence of oxygen. This phenomenon is called 'aerobic glycolysis'. Also, glucose level is found lower in tumor environment. Leukemia is characterized by abnormal proliferation of hematopoietic cells. STAT3 a transcription factor and an oncogene is upregulated in many tumor types. Despite its well-defined functions, STAT3 has also been proposed as a metabolic regulator. In this study, we aimed to determine the role STAT3 activation in glucose limitation, in leukemia cell lines. K562, NB-4 and HL-60 cells were found sensitive to glucose limitation. In low glucose conditions, total and nuclear STAT3 protein was decreased in all cells. In mitochondria, S727 phosphorylated STAT3 (mitochondrial form) was determined slightly increased in K562 and NB-4 cells. On the other side, ectopically STAT3 expressing cells had increased glucose consumption and less proliferated in low glucose medium. This data suggests that aerobic glycolysis might be upregulated upon STAT3 expression in leukemia cells, in glucose limitation. Furthermore, in this study, it was found that GLUT3 expressing cells did not reduce STAT3 expression in low glucose medium. GLUT3 was previously determined as a molecular marker for cell sensitivity to glucose limitation, therefore, it could be hypothesized as GLUT3 expressing cells might not need to alter STAT3 expression in low glucose level. Overall, our data suggest that leukemia cells rewire glucose metabolism via STAT3 expression in glucose limitation. Elucidating pathways that cause differential phosphorylation of STAT3 and its interaction with other energy regulating pathways in cellular response to glucose limitation might be beneficial to design new drug targets such as STAT3 inhibitors for leukemia treatment.


Asunto(s)
Glucosa/metabolismo , Leucemia/metabolismo , Factor de Transcripción STAT3/metabolismo , Línea Celular Tumoral , Proliferación Celular , Medios de Cultivo/química , Regulación hacia Abajo , Regulación Leucémica de la Expresión Génica , Transportador de Glucosa de Tipo 3/metabolismo , Glucólisis/fisiología , Células HL-60 , Humanos , Células K562 , Leucemia/genética , Leucemia/patología , Mitocondrias/metabolismo , Factor de Transcripción STAT3/genética
16.
Environ Toxicol ; 37(1): 131-141, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34664771

RESUMEN

Bisphenol A (BPA) is an estrogen-like compound, and an environmental hormone, that is commonly used in daily life. Therefore, it may enter the human body through food or direct contact, causing BPA residues in blood and urine. Because most studies focused on the analysis of BPA in reproductive cells or tissues, regarding evidence the effect of BPA on human retinal pigment epithelium (ARPE-19) cells unavailable. Accordingly, the present study explored the cytotoxicity of BPA on ARPE-19 cells. After BPA treatment, the expression of Bcl-XL an antiapoptotic protein, in the mitochondria decreased, and the expression of Bax, a proapoptotic protein increased. Then the mitochondrial membrane potential was affected. BPA changed in mitochondrial membrane potential led to the release of cytochrome C, which activated caspase-9 to promote downstream caspase-3 leading to cytotoxicity. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase 1 (HO-1) pathway play a major role in age-related macular degeneration. Our results showed that expression of HO-1 and Nrf2 suppressed by BPA. Superoxide dismutase and catalase, which Nrf2 downstream antioxidants, were degraded by BPA. AMP-activated kinase (AMPK), which can regulate the phosphorylation of Nrf2, and the phosphorylation of AMPK expression was reduced by BPA. Finally, BPA-induced ROS generation and cytotoxicity were reduced by N-acetyl-l-cysteine. Taken together, these results suggest that BPA induced ARPE-19 cells via oxidative stress, which was associated with down regulated Nrf2/HO-1 pathway, and the mitochondria dependent apoptotic signaling pathway.


Asunto(s)
Hemo-Oxigenasa 1 , Factor 2 Relacionado con NF-E2 , Antioxidantes/metabolismo , Apoptosis , Compuestos de Bencidrilo , Supervivencia Celular , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Humanos , Mitocondrias/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Fenoles , Epitelio Pigmentado de la Retina/metabolismo
17.
Food Chem ; 373(Pt A): 131389, 2022 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-34710690

RESUMEN

Reactive oxygen species (ROS) are mitochondrial respiration byproducts, the accumulation of which may cause oxidative damage and is associated with several chronic health problems. As an essential unsaturated fatty acid, eicosapentaenoic acid (EPA) provides various physiological functions; however, its exact regulatory role remains elusive. The current study aimed to address how EPA regulates cellular antioxidant capacity and the possible mechanisms of action. Upon 48 h of EPA treatment, the ROS levels of HepG2 cells were reduced by at least 40%; the total cellular antioxidant capacity was increased by approximately 50-70%, accompanied by enhanced activities and expression of major antioxidant enzymes. Furthermore, the mitochondrial membrane potential and the mitochondrial biogenesis were dramatically improved in EPA-treated cells. These data suggest that EPA improves cellular antioxidant capacity by enhancing mitochondrial function and biogenesis, which sheds light on EPA as a dietary complement to relieve the oxidative damage caused by chronic diseases.


Asunto(s)
Antioxidantes , Ácido Eicosapentaenoico , Antioxidantes/metabolismo , Ácido Eicosapentaenoico/metabolismo , Mitocondrias/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo
18.
Sci Total Environ ; 806(Pt 3): 151228, 2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-34715218

RESUMEN

Environmental hypoxic hazard has increasingly become a global public health issue, with impelling evidences supporting the relation between hypoxia and cognitive disorders. As a potent stressor, hypoxia causes mitochondrial dysfunction with insufficient energy production, thus the formation of brain memory disorder. Yet, the underlying molecular mechanism/s against hypoxia induced injury have yet to be identified. Here, we report that cold inducible RNA binding protein (Cirbp) attenuates hypoxia induced insufficient energy production and oxidative stress. Further analyses show that Cirbp sustains protein levels of respiratory chain complexes II (SDHB) and IV (MT-CO1), and directly binds the 3'UTR of Atp5g3 to control mitochondrial homeostasis and ATP biogenesis upon hypoxic stress. Altogether, our data establish Cirbp as a critical protective factor against hypoxic health hazard and provide novel insights into its latent regulation network.


Asunto(s)
Hipoxia , Proteínas de Unión al ARN , Encéfalo/metabolismo , Humanos , Trastornos de la Memoria , Mitocondrias/metabolismo , Proteínas de Unión al ARN/metabolismo
19.
Nutrition ; 93: 111412, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34749061

RESUMEN

OBJECTIVES: Skeletal muscle accounts for 80% of whole body insulin-stimulated glucose uptake, and it plays a key role in preventing and curing obesity and insulin resistance (IR). Vitamin K2 (VK2) plays a beneficial role in improving mitochondrial function through SIRT1 signaling in high-fat diet (HFD)-induced mice and palmitate acid (PA)-treated C2C12 cells. A previous study also found VK2 increases oxidative muscle fibers and decreases glycolytic muscle fibers in obesity-induced mice, however, the underlying molecular mechanism of effect of VK2 on increasing oxidative fibers have not been well established. METHODS: C57BL/6 male mice were induced IR using HFD fed. Animals received HFD for eight weeks, and different doses of VK2 were supplemented by oral gavage for the last eight weeks were randomly and equally divided into seven groups. C2C12 cells were exposed to different doses of PA for 16 h to mimic insulin resistance in vivo. Skeletal muscle types and mitochondrial function evaluated. C2C12 cells were transfected with SIRT1 siRNA. RESULTS: The present study first revealed that VK2 intervention also alleviated plasma non-esterified fatty acid levels that contribute to obesity-induced IR, VK2 administration also could effectively increase the proportion of slow-twitch fibers by improving mitochondrial function via SIRT1 signaling pathway in both HFD-fed mice and PA-exposed cells. However, the benefits of VK2 were abrogated in C2C12 transfected with SIRT1 siRNA in PA-treated C2C12 cells. Thus, SIRT1 is partially required for VK2 improvement the proportion of slow-twitch fiber in PA-treated C2C12 cells. CONCLUSION: Naturally occurring VK2 increases slow-twitch fibers by improving mitochondrial function and decreasing non-esterified fatty acid levels via partially SIRT1/SIRT3 signaling pathway. These data have potential importance for the therapy for a number of muscular and neuromuscular diseases in humans.


Asunto(s)
Resistencia a la Insulina , Sirtuina 3 , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Dieta Alta en Grasa/efectos adversos , Masculino , Ratones , Ratones Endogámicos C57BL , Mitocondrias/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares de Contracción Lenta/metabolismo , Músculo Esquelético/metabolismo , Transducción de Señal , Sirtuina 1/genética , Sirtuina 1/metabolismo , Sirtuina 3/metabolismo , Vitamina K 2
20.
Artículo en Inglés | MEDLINE | ID: mdl-34517131

RESUMEN

Non-shivering thermogenesis (NST) is a heat generating process controlled by the mitochondria of brown adipose tissue (BAT). In the recent decade, 'functionally' acting brown adipocytes in white adipose tissue (WAT) has been identified as well: the so-called process of the 'browning' of WAT. While the importance of uncoupling protein 1 (UCP1)-oriented mitochondrial activation has been intensely studied, the role of peroxisomes during the browning of white adipocytes is poorly understood. Here, we assess the change in peroxisomal membrane proteins, or peroxins (PEXs), during cold stimulation and importantly, the role of PEX13 in the cold-induced remodeling of white adipocytes. PEX13, a protein that originally functions as a docking factor and is involved in protein import into peroxisome matrix, was highly increased during cold-induced recruitment of beige adipocytes within the inguinal WAT of C57BL/6 mice. Moreover, beige-induced 3 T3-L1 adipocytes and stromal vascular fraction (SVF) cells by exposure to the peroxisome proliferator-activated receptor gamma (PPARγ) agonist rosiglitazone showed a significant increase in mitochondrial thermogenic factors along with peroxisomal proteins including PEX13, and these were confirmed in SVF cells with the beta 3 adrenergic receptor (ß3AR)-selective agonist CL316,243. To verify the relevance of PEX13, we used the RNA silencing method targeting the Pex13 gene and evaluated the subsequent beige development in SVF cells. Interestingly, siPex13 treatment suppressed expression of thermogenic proteins such as UCP1 and PPARγ coactivator 1 alpha (PGC1α). Overall, our data provide evidence supporting the role of peroxisomal proteins, in particular PEX13, during beige remodeling of white adipocytes.


Asunto(s)
Tejido Adiposo Blanco/metabolismo , Proteínas de la Membrana/genética , PPAR gamma/genética , Termogénesis/genética , Proteína Desacopladora 1/genética , Células 3T3-L1 , Tejido Adiposo Pardo/metabolismo , Agonistas de Receptores Adrenérgicos beta 3/farmacología , Animales , Dioxoles/farmacología , Ratones , Mitocondrias/genética , Mitocondrias/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Peroxisomas/genética , Interferencia de ARN , Receptores Adrenérgicos beta 3/genética , /metabolismo
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