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SIRT1 is required for mitochondrial biogenesis reprogramming in hypoxic human pulmonary arteriolar smooth muscle cells
| Content Provider | Semantic Scholar |
|---|---|
| Author | Li, Pengyun Liu, Yan Ju Burns, Nana Zhao, Ke-Seng Song, Rui |
| Copyright Year | 2017 |
| Abstract | Although recent studies have reported that mitochondria are putative oxygen sensors underlying hypoxic pulmonary vasoconstriction, little is known concerning the sirtuin 1 (SIRT1)-mediated mitochondrial biogenesis regulatory program in pulmonary arteriolar smooth muscle cells (PASMCs) during hypoxia/reoxygenation (H/R). We investigated the epigenetic regulatory mechanism of mitochondrial biogenesis and function in human PASMCs during H/R. Human PASMCs were exposed to hypoxia of 24-48 h and reoxygenation of 24-48 h. The expression of SIRT1 was reduced in a time-dependent manner. Mitochondrial transcription factor A (TFAM) expression was increased during hypoxia and decreased during reoxygenation, while the release of TFAM was increased in a time-dependent manner. Lentiviral overexpression of SIRT1 preserved SIRT3 deacetylase activity in human PASMCs exposed to H/R. Knockdown of PGC-1α suppressed the effect of SIRT1 on SIRT3 activity. Knockdown of SIRT3 abrogated SIRT1-mediated deacetylation of cyclophilin D (CyPD). Notably, knockdown of SIRT3 or PGC-1α suppressed the incremental effect of SIRT1 on mitochondrial TFAM, mitochondrial DNA (mtDNA) content and cellular ATP levels. Importantly, polydatin restored SIRT1 levels in human PASMCs exposed to H/R. Knockdown of SIRT1 suppressed the effect of polydatin on mitochondrial TFAM, mtDNA content and cellular ATP levels. In conclusion, SIRT1 expression is decreased in human PASMCs during H/R. TFAM expression in mitochondria is reduced and the release of TFAM is increased by H/R. PGC-1α/SIRT3/CyPD mediates the protective effect of SIRT1 on expression and release of TFAM and mitochondrial biogenesis and function. Polydatin improves mitochondrial biogenesis and function by enhancing SIRT1 expression in hypoxic human PASMCs. |
| Starting Page | 1127 |
| Ending Page | 1136 |
| Page Count | 10 |
| File Format | PDF HTM / HTML |
| PubMed reference number | 28339017 |
| Alternate Webpage(s) | https://doi.org/10.3892/ijmm.2017.2932 |
| DOI | 10.3892/ijmm.2017.2932 |
| Journal | International journal of molecular medicine |
| Volume Number | 39 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adenosine Triphosphate Biologic Preservation DNA, Mitochondrial Deacetylation Hypoxia Increment Mitochondrial Biogenesis Mitochondrial Diseases Muscle Cells Myocytes, Smooth Muscle Oxygen Reprogram SIRT1 gene Smooth muscle (tissue) TFAM gene TRANSCRIPTION FACTOR Vascular constriction (function) cyclophilin D deacetylase activity polydatin study of epigenetics |
| Content Type | Text |
| Resource Type | Article |
