The goal of the present study was to determine the role of calpain in changes in plasma membrane permeability and cytoskeleton-associated paxillin, vinculin, talin, and α-actinin levels during acute renal cell death. The mitochondrial inhibitor antimycin A or hypoxia produced graded plasma membrane permeability in renal proximal tubules (RPTs), first allowing propidium iodide (PI, molecular mass 668 Da) influx and then lactate dehydrogenase (LDH, molecular mass 130 kDa) release. Cytoskeleton-associated paxillin levels decreased concomitantly with PI influx and before LDH release, whereas cytoskeleton-associated talin and vinculin levels decreased concomitantly with LDH release. Cytoskeleton-associated α-actinin levels did not change during antimycin A exposure or hypoxia. Purified μ-calpain cleaved paxillin, talin, vinculin, but not α-actinin. The dissimilar calpain inhibitors 3-(4-iodophenyl)-2-mercapto-(Z)-2-propenoic acid (PD150606) or chloroacetic acid N′-[6,7-dichloro-4-phenyl)-3-oxo-3,4-dihydroquinoxalin-2-yl] hydrazide (SJA7029) preserved cytoskeleton-associated paxillin, talin, and vinculin levels and prevented PI influx and LDH release in antimycin A-exposed or hypoxic RPTs. These results suggest that calpain mediates increased plasma membrane permeability and hydrolysis of cytoskeleton-associated paxillin, vinculin, and talin during renal cell death.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - Jan 1 2003|
ASJC Scopus subject areas
- Molecular Medicine