FEBS Letters
Volume 582, Issue 19 , Pages 2857-2862, 20 August 2008

SIRT2 is a negative regulator of anoxia–reoxygenation tolerance via regulation of 14-3-3 ζ and BAD in H9c2 cells

Edited by Robert Barouki

Translational Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1454, United States

Received 18 April 2008; received in revised form 3 July 2008; accepted 7 July 2008. published online 18 July 2008.

Abstract 

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.

Keywords: SIRT2, BAD, 14-3-3 ζ, H9c2 cells, Anoxia–reoxygenation

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PII: S0014-5793(08)00596-6

doi:10.1016/j.febslet.2008.07.016

FEBS Letters
Volume 582, Issue 19 , Pages 2857-2862, 20 August 2008