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- Title
Genetic depletion of SirT2 augments cell survival after hypoxiareoxygenation injury.
- Authors
Lynn, Edward G.; McLeod, Christopher J.; Sack, Michael N.
- Abstract
Ischemic preconditioning (IPC) is a biological phenomenon whereby transient ischemic episodes orchestrate subsequent cellular tolerance to ischemic and oxidative stress. In light of their putative 'cytoprotective properties', we evaluated the expression pattern of sirtuins in response to IPC in rat heart: SirT2 mRNA was significantly down-regulated by IPC. To evaluate the functional significance of this observation, we investigate the role of SirT2 in hypoxia-reoxygenation injury. Rat cardiac derived H9c2 cells exposed to 17-h hypoxia and 2-h reoxygenation 48-h post-transfection with SirT2 siRNA exhibited increased cell survival. Conversely SirT2 overexpression decreased cell survival. Affymetrix gene-chip analysis identified the adaptor protein 14-3-3-zeta as one of four candidate cytoprotective genes up-regulated in response to SirT2 RNAi. Steady-state protein levels confirm 14-3-3-zeta induction following SirT2 depletion. SirT2-depleted H9c2 also exhibited increased association of 14-3-3-zeta with the pro-apoptotic protein Bad. The current study indicates SirT2 RNAi bestows resistance to hypoxia-reoxygenation injury in H9c2 via a mechanism involving 14-3-3-zeta interacting with Bad.
- Subjects
GENES; OXIDATIVE stress; ENZYMES; LABORATORY rats; CELLS
- Publication
FASEB Journal, 2007, Vol 21, Issue 5, pA666
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fasebj.21.5.a666-c