SIRT5: a safeguard against oxidative stress-induced apoptosis in cardiomyocytes

Cell Physiol Biochem. 2013;32(4):1050-9. doi: 10.1159/000354505. Epub 2013 Oct 31.

Abstract

Background: SIRT5 is located in the mitochondria, and plays a crucial role in the regulation of metabolic process and cellular apoptosis. Cardiomyocytes are abundant in mitochondria. However, the role of SIRT5 in oxidative stress-induced apoptosis is still unknown in cardiomyocytes.

Methods and results: Western blots analysis revealed that SIRT5 is significantly down-regulated in cardiomyocytes upon oxidative stress. MTT assay, DAPI staining, and caspase 3/7 activity assay were used to estimate apoptosis development. The result suggested that compared with the wild-type group, SIRT5 knockdown results in a marked reduction in cell viability, and a significant increase in the number of apoptotic cells and the caspase 3/7 activity. Protein immunoprecipitation revealed a direct interaction between Bcl-Xl and SIRT5. Apoptosis assay and western blot anaylsis suggested that SIRT5 levels could affect the levels of Bcl-Xl expression, but have no effect on the apoptosis development in Bcl-Xl knockdown cells.

Conclusion: This study reveals a novel role of SIRT5 in the regulation of oxidative stress-induced apoptosis in cardiomyocytes. Pharmacological interventions on SIRT5 expression may be useful in the treatment of oxidative stress-related cardiac injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 7 / genetics
  • Caspase 7 / metabolism
  • Cell Line
  • Cell Survival / drug effects
  • Cells, Cultured
  • Hydrogen Peroxide / pharmacology
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism*
  • Oxidative Stress / drug effects
  • Rats
  • Sirtuins / genetics
  • Sirtuins / metabolism*
  • bcl-X Protein / genetics
  • bcl-X Protein / metabolism

Substances

  • bcl-X Protein
  • Hydrogen Peroxide
  • Caspase 3
  • Caspase 7
  • SIRT5 protein, rat
  • Sirtuins