First Author | Heo KS | Year | 2011 |
Journal | J Cell Biol | Volume | 193 |
Issue | 5 | Pages | 867-84 |
PubMed ID | 21624955 | Mgi Jnum | J:172726 |
Mgi Id | MGI:5008672 | Doi | 10.1083/jcb.201010051 |
Citation | Heo KS, et al. (2011) PKC{zeta} mediates disturbed flow-induced endothelial apoptosis via p53 SUMOylation. J Cell Biol 193(5):867-84 |
abstractText | Atherosclerosis is readily observed in regions of blood vessels where disturbed blood flow (d-flow) is known to occur. A positive correlation between protein kinase C zeta (PKCzeta) activation and d-flow has been reported, but the exact role of d-flow-mediated PKCzeta activation in atherosclerosis remains unclear. We tested the hypothesis that PKCzeta activation by d-flow induces endothelial cell (EC) apoptosis by regulating p53. We found that d-flow-mediated peroxynitrite (ONOO(-)) increased PKCzeta activation, which subsequently induced p53 SUMOylation, p53-Bcl-2 binding, and EC apoptosis. Both d-flow and ONOO(-) increased the association of PKCzeta with protein inhibitor of activated STATy (PIASy) via the Siz/PIAS-RING domain (amino acids 301-410) of PIASy, and overexpression of this domain of PIASy disrupted the PKCzeta-PIASy interaction and PKCzeta-mediated p53 SUMOylation. En face confocal microscopy revealed increases in nonnuclear p53 expression, nitrotyrosine staining, and apoptosis in aortic EC located in d-flow areas in wild-type mice, but these effects were significantly decreased in p53(-/-) mice. We propose a novel mechanism for p53 SUMOylation mediated by the PKCzeta-PIASy interaction during d-flow-mediated EC apoptosis, which has potential relevance to early events of atherosclerosis. |