Sirtuin 6 protects the heart from hypoxic damage

Anna Maksin-Matveev, Yariv Kanfi, Edith Hochhauser, Ahuva Isak, Haim Y. Cohen, Asher Shainberg

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Sirtuin 6 (SIRT6) is a protein associated with prolonged life expectancy. We investigated whether life extension is associated with cardioprotection against hypoxia. The proposed study is to develop approaches to reduce hypoxic damage through the use of the sirtuin pathway and to elucidate the mechanism involved. For that purpose we subjected cardiomyocytes from transgenic mice (TG) with over-expression of SIRT6, to hypoxic stress in cell cultures. We hypothesized that cardiomyocytes from transgenic mice subjected to prolonged hypoxia may release survival factors or fewer damage markers to protect them from hypoxic stress compared with wild type (WT) mice. Lactate dehydrogenase (LDH) and creatine kinase (CK) released to the medium and propidium iodide (PI) binding, were markedly decreased following hypoxia in TG cardiomyocytes. The protective mechanism of SIRT6 over-expression includes the activation of pAMPKα pathway, the increased protein level of B-cell lymphoma 2 (Bcl2), the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), the decrease of reactive oxygen species (ROS) and the reduction in the protein level of phospho-protein kinase B (pAkt) during hypoxia. Together, all these processes impede the necrosis/apoptosis pathways leading to the improved survival of cardiomyocytes following hypoxia, which might explain life extension.

Original languageEnglish
Pages (from-to)81-90
Number of pages10
JournalExperimental Cell Research
Volume330
Issue number1
DOIs
StatePublished - 1 Jan 2015
Externally publishedYes

Keywords

  • Cardiac cell cultures
  • Cardioprotection
  • Hypoxia
  • Over-expression of Sirtuin 6

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