Premium
SIRT2 is a negative regulator of anoxia–reoxygenation tolerance via regulation of 14‐3‐3 ζ and BAD in H9c2 cells
Author(s) -
Lynn Edward G.,
McLeod Christopher J.,
Gordon Jeffrey P.,
Bao Jianjun,
Sack Michael N.
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.07.016
Subject(s) - sirt2 , gene knockdown , microbiology and biotechnology , regulator , phenotype , cytosol , biology , gene , chemistry , sirtuin , genetics , biochemistry , enzyme , acetylation
Knockdown or inhibition of SIRT2 enhances biological stress‐tolerance. We extend this phenotype showing that SIRT2 knockdown reduces anoxia–reoxygenation injury in H9c2 cells. Gene array analysis following SIRT2 siRNA knockdown identifies 14‐3‐3 ζ as the most robustly induced gene. SIRT2 knockdown evokes induction of this chaperone, facilitating cytosolic sequestration of BAD with a corresponding reduction in mitochondrial BAD localization. Concurrent siRNA against SIRT2 and 14‐3‐3 ζ abolishes the SIRT2‐depleted cytoprotective phenotype. SIRT2 functions to moderate cellular stress‐tolerance, in part, by modulating the levels of 14‐3‐3 ζ with the concordant control of BAD subcellular localization.