SIRT2 is a negative regulator of anoxia-reoxygenation tolerance via regulation of 14-3-3 zeta and BAD in H9c2 cells.
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 zeta 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 zeta abolishes the SIRT2-depleted cytoprotective phenotype. SIRT2 functions to moderate cellular stress-tolerance, in part, by modulating the levels of 14-3-3 zeta with the concordant control of BAD subcellular localization.
Lynn
Edward G
EG
Translational Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1454, USA. .
McLeod
Christopher J
CJ
Gordon
Jeffrey P
JP
Bao
Jianjun
J
Sack
Michael N
MN
D048948:14-3-3 Proteins / Q000235:genetics* / Q000378:metabolism; D000693:Anaerobiosis / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D003593:Cytoplasm / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D032342:Muscle Cells / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D056565:Sirtuin 2; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D051025:bcl-Associated Death Protein / Q000378:metabolism*
D048948:14-3-3 Proteins; C494821:Bad protein, rat; D034741:RNA, Small Interfering; C097475:Sirt2 protein, rat; D051025:bcl-Associated Death Protein; D056565:Sirtuin 2; D037761:Sirtuins; D010100:Oxygen