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

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