Metformin protects high glucose‑cultured cardiomyocytes from oxidative stress by promoting NDUFA13 expression and mitochondrial biogenesis via the AMPK signaling pathway
| Autor: | Li‑Li Wan, Xuebo Liu, Yu Zhao, Xiang‑Dong Liu, Ya‑Guang Bi, Yong‑Guang Li, Meng Wei, Qingyong Zhang, Mei‑Ling Yan, Guangyu Wang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research NDUFA13 mitochondrial biogenesis cardiomyocyte AMP-Activated Protein Kinases medicine.disease_cause Biochemistry 0302 clinical medicine Myocytes Cardiac reactive oxygen species chemistry.chemical_classification Organelle Biogenesis Chemistry Articles Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Metformin Mitochondria Cell biology Mitochondrial respiratory chain Oncology 030220 oncology & carcinogenesis Molecular Medicine Signal Transduction medicine.drug China Cell Survival Protein Serine-Threonine Kinases Cell Line Mitochondrial Proteins 03 medical and health sciences Genetics medicine Animals Molecular Biology Reactive oxygen species Electron Transport Complex I Superoxide Dismutase AMPK Rats Oxidative Stress Glucose 030104 developmental biology Mitochondrial biogenesis Hyperglycemia Organelle biogenesis Oxidative stress Molecular Chaperones Transcription Factors |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| Popis: | Tissue damage in diabetes is at least partly due to elevated reactive oxygen species production by the mitochondrial respiratory chain during hyperglycemia. Sustained hyperglycemia results in mitochondrial dysfunction and the abnormal expression of mitochondrial genes, such as NADH: Ubiquinone oxidoreductase subunit A13 (NDUFA13). Metformin, an AMP‑activated protein kinase (AMPK) activator, protects cardiomyocytes from oxidative stress by improving mitochondrial function; however, the exact underlying mechanisms are not completely understood. The aim of the present study was to investigated the molecular changes and related regulatory mechanisms in the response of H9C2 cardiomyocytes to metformin under high glucose conditions. H9C2 cells were subjected to CCK‑8 assay to assess cell viability. Reactive oxygen species generation was measured with DCFH‑DA assay. Western blotting was used to analyze the expression levels of NDUFA13, AMPK, p‑AMPK and GAPDH. Reverse transcription‑quantitative PCR was used to evaluate the expression levels of mitochondrial genes and transcription factors. It was observed that metformin protected H9C2 cardiomyocytes by suppressing high glucose (HG)‑induced elevated oxidative stress. In addition, metformin stimulated mitochondrial biogenesis, as indicated by increased expression levels of mitochondrial genes (NDUFA1, NDUFA2, NDUFA13 and manganese superoxide dismutase) and mitochondrial biogenesis‑related transcription factors [peroxisome proliferator‑activated receptor‑gamma coactivator‑1α, nuclear respiratory factor (NRF)‑1, and NRF‑2] in the metformin + HG group compared with the HG group. Moreover, metformin promoted mitochondrial NDUFA13 protein expression via the AMPK signaling pathway, which was abolished by pretreatment with the AMPK inhibitor, Compound C. The results suggested that metformin protected cardiomyocytes against HG‑induced oxidative stress via a mechanism involving AMPK, NDUFA13 and mitochondrial biogenesis. |
| Databáze: | OpenAIRE |
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