PT  - JOURNAL ARTICLE
AU  - Liu, Xiuli
AU  - Schnellmann, Rick G.
TI  - Calpain Mediates Progressive Plasma Membrane Permeability and Proteolysis of Cytoskeleton-Associated Paxillin, Talin, and Vinculin during Renal Cell Death
AID  - 10.1124/jpet.102.043406
DP  - 2003 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 63--70
VI  - 304
IP  - 1
4099  - http://jpet.aspetjournals.org/content/304/1/63.short
4100  - http://jpet.aspetjournals.org/content/304/1/63.full
SO  - J Pharmacol Exp Ther2003 Jan 01; 304
AB  - 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 acidN′-[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. The American Society for Pharmacology and Experimental Therapeutics