Induction of protein disulfide isomerase mRNA by Delta(12)-prostaglandin J(2)

Protein disulfide isomerase (PDI) catalyzes the correct protein disulfide formation and is a key regulator for protein folding. We examined the effect of Delta(12)-prostaglandin (PG) J(2), a thiol-reactive tress PG, on the expression of the PDI gene. Delta(12)-PGJ(2) transiently induced the PDI mRNA in HeLa cells. Other stress inducers, tunicamycin, A23187, and heat shock, which caused an accumulation of unfolded proteins, also induced the PDI mRNA, indicating that the unfolded protein accumulation response induces PDI gene expression. Cycloheximide by itself strongly induced the PDI mRNA, but did not inhibit the effect of Delta(12)-PGJ(2), suggesting that the pathway of Delta(12)-PGJ(2)-induced PDI gene expression does not involve unfolded protein accumulation. On the other hand, dithiothreitol, a reducing agent, induced the PDI mRNA, and Delta(12)-PGJ(2) did not exert additive induction. Thus, Delta(12)-PGJ(2) induces PDI gene expression through a pathway independent of de novo protein synthesis. (C) 1996 Academic Press, Inc.