ORP150/HSP12A protects renal tubular epithelium from ischemia-induced cell death

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Yoshio BandoS Ogawa

Abstract

The 150 kDa oxygen-regulated protein (ORP150) is an inducible endoplasmic reticulum (ER) chaperone with cytoprotective properties in settings of cell stress, such as ischemia/reperfusion (I/R). Renal tissue from patients with acute renal failure displayed strong induction of ORP150 in tubular epithelium. In a rodent model of renal I/R injury, ORP150 was expressed in both the ischemic and contralateral kidney, principally in the thick ascending loop of Henle (TAL) and distal tubules. Cultured renal epithelial cells exposed to hypoxic or hyperosmotic conditions displayed induction of ORP150. Renal tubular epithelial cells stably transfected with ORP150 sense or antisense cDNA displayed a strong correlation between ORP150 expression and vulnerability to hypoxic/osmotic stress; higher levels of ORP150 were protective, whereas lower levels increased susceptibility to cell death. Compared with nontransgenic controls, transgenic mice overexpressing ORP150 subjected to renal I/R displayed a blunted rise of serum creatinine and blood urea nitrogen, and enhanced survival of TAL, consistent with cytoprotection. In contrast, heterozygous ORP150+/- mice, with lower levels of ORP150, showed enhanced renal injury. These data are consistent wi...Continue Reading

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