INDUCTION OF THE GLUCOSE-REGULATED PROTEINS BY CA2-ATPASE INHIBITORS AND BREFELDIN-A()

Glucose-regulated proteins (grp's) are a group of stress proteins whos e syntheses are greatly enhanced when cells are exposed to stressful c onditions including glucose stravation and Ca2+ ionophore which pertur bs intracellular Ca2+ homeostasis, In this study, we examined the abil ity of endomembrane Ca2+-ATPase inhibitors, thapsigargin, 2,5-di(tert- butyl)-1,4-hydroquinone and cyclopiazonic acid, and brefeldin A, an in hibitor of intracellular protein transport, as inducers of grp's, The treatment of either Ca2+-ATPase inhibitors or brefeldin A markedly inc reased the syntheses of grp's, whereas BAPTA-AM, a cell permeant Ca2chelator, did not induce the gtp's. In addition,grp induction by Ca2+- ATPase inhibitors was not inhibited by BAPTA-AM preloading which block ed increases in cytosolic Ca2+, resulting from Ca2+-ATPase inhibitor t reatment, Thus, these results indicate that grp expression is closely coupled to the depletion of the intracellular Ca2+ store as well as pr otein trafficking from the endoplasmic reticulum to Golgi.