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SIRT1 is required for mitochondrial biogenesis reprogramming in hypoxic human pulmonary arteriolar smooth muscle cells

  • Authors:
    • Pengyun Li
    • Yan Liu
    • Nana Burns
    • Ke-Seng Zhao
    • Rui Song
  • View Affiliations / Copyright

    Affiliations: Guangdong Key Laboratory of Shock and Microcirculation Research, Department of Pathophysiology, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Pharmacy, Henan Medical College, Zhengzhou, Henan 450046, P.R. China, Department of Pediatrics, University of Colorado Denver, Aurora, CO 80045, USA
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1127-1136
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    Published online on: March 22, 2017
       https://doi.org/10.3892/ijmm.2017.2932
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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.
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Copy and paste a formatted citation
Spandidos Publications style
Li P, Liu Y, Burns N, Zhao K and Song R: SIRT1 is required for mitochondrial biogenesis reprogramming in hypoxic human pulmonary arteriolar smooth muscle cells. Int J Mol Med 39: 1127-1136, 2017.
APA
Li, P., Liu, Y., Burns, N., Zhao, K., & Song, R. (2017). SIRT1 is required for mitochondrial biogenesis reprogramming in hypoxic human pulmonary arteriolar smooth muscle cells. International Journal of Molecular Medicine, 39, 1127-1136. https://doi.org/10.3892/ijmm.2017.2932
MLA
Li, P., Liu, Y., Burns, N., Zhao, K., Song, R."SIRT1 is required for mitochondrial biogenesis reprogramming in hypoxic human pulmonary arteriolar smooth muscle cells". International Journal of Molecular Medicine 39.5 (2017): 1127-1136.
Chicago
Li, P., Liu, Y., Burns, N., Zhao, K., Song, R."SIRT1 is required for mitochondrial biogenesis reprogramming in hypoxic human pulmonary arteriolar smooth muscle cells". International Journal of Molecular Medicine 39, no. 5 (2017): 1127-1136. https://doi.org/10.3892/ijmm.2017.2932
Copy and paste a formatted citation
x
Spandidos Publications style
Li P, Liu Y, Burns N, Zhao K and Song R: SIRT1 is required for mitochondrial biogenesis reprogramming in hypoxic human pulmonary arteriolar smooth muscle cells. Int J Mol Med 39: 1127-1136, 2017.
APA
Li, P., Liu, Y., Burns, N., Zhao, K., & Song, R. (2017). SIRT1 is required for mitochondrial biogenesis reprogramming in hypoxic human pulmonary arteriolar smooth muscle cells. International Journal of Molecular Medicine, 39, 1127-1136. https://doi.org/10.3892/ijmm.2017.2932
MLA
Li, P., Liu, Y., Burns, N., Zhao, K., Song, R."SIRT1 is required for mitochondrial biogenesis reprogramming in hypoxic human pulmonary arteriolar smooth muscle cells". International Journal of Molecular Medicine 39.5 (2017): 1127-1136.
Chicago
Li, P., Liu, Y., Burns, N., Zhao, K., Song, R."SIRT1 is required for mitochondrial biogenesis reprogramming in hypoxic human pulmonary arteriolar smooth muscle cells". International Journal of Molecular Medicine 39, no. 5 (2017): 1127-1136. https://doi.org/10.3892/ijmm.2017.2932
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