title: Sirtuin 6 protects the heart from hypoxic damage.
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.
authors: The Mina and Everard Goodman, Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
authors: Anna
authors: A
authors: Maksin-Matveev
authors: The Mina and Everard Goodman, Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
authors: Yariv
authors: Y
authors: Kanfi
authors: The Laboratory of the Department of Cardiothoracic Surgery, Felsenstein Medical Research Center, Rabin Medical Center, Petach Tikva, Israel.
authors: Edith
authors: E
authors: Hochhauser
authors: The Mina and Everard Goodman, Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
authors: Ahuva
authors: A
authors: Isak
authors: The Mina and Everard Goodman, Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel.
authors: Haim Y
authors: HY
authors: Cohen
authors: The Mina and Everard Goodman, Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel. Electronic address: asher.shainberg@gmail.com.
authors: Asher
authors: A
authors: Shainberg
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia; D002478:Cells, Cultured; D051379:Mice; D032383:Myocytes, Cardiac / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C052617:Bcl2 protein, mouse; C501860:Sirt6 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D037761:Sirtuins
keywords: Cardiac cell cultures; Cardioprotection; Hypoxia; Over-expression of Sirtuin 6