Extracellular signal-regulated kinase activation during renal ischemia/reperfusion mediates focal adhesion dissolution and renal injury

被引:56
作者
Alderliesten, Maaike [1 ]
de Graauw, Marjo [1 ]
Oldenampsen, Judith [1 ]
Qin, Yu [1 ]
Pont, Chantal [1 ]
van Buren, Liesbeth [1 ]
van de Water, Bob [1 ]
机构
[1] Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Toxicol, NL-2300 RA Leiden, Netherlands
关键词
D O I
10.2353/ajpath.2007.060805
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Acute renal failure due to ischemia/reperfusion involves disruption of integrin-mediated. cellular adhesion and activation of the extracellular signal-regulated kinase (ERK) pathway. The dynamics of focal adhesion organization and phosphorylation during ischemia/ reperfusion in relation to ERK activation are unknown. in control kidneys, protein tyrosine-rich focal adhesions, containing focal adhesion kinase, paxillin, and talin, were present at the basolateral membrane of tubular cells and colocalized with short F-actin stress fibers. Unilateral renal ischemia/reperfusion caused a reversible protein dephosphorylation and loss of focal adhesions. The focal adhesion protein phosphorylation rebounded in a biphasic manner, in association with increased focal adhesion kinase, Src, and paxillin tyrosine phosphorylation. Preceding phosphorylation of these focal adhesion proteins, reperfusion caused increased phosphorylation of ERK The specific mitogen-activated protein kinase kinase 1/2 inhibitor U0126 prevented ERK activation and attenuated focal adhesion kinase, paxillin, and Src phosphorylation, focal adhesion restructuring, and ischemia/reperfusion-induced renal injury. We propose a model whereby ERK activation enhanced protein tyrosine phosphorylation during ischemia/reperfusion, thereby driving the dynamic dissolution and restructuring of focal adhesions and F-actin cytoskeleton during reperfusion and renal injury.
引用
收藏
页码:452 / 462
页数:11
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