Induction of protein disulfide isomerase mRNA by delta 12-prostaglandin J2.
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) J2, a thiol-reactive stress PG, on the expression of the PDI gene. Delta 12-PGJ2 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-PGJ2, suggesting that the pathway of delta 12-PGJ2-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-PGJ2 did not exert additive induction. Thus, delta 12-PGJ2 induces PDI gene expression through a pathway independent of de novo protein synthesis.
Odani
N
N
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Negishi
M
M
Takahashi
S
S
Ichikawa
A
A
D000001:Calcimycin / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004790:Enzyme Induction; D015870:Gene Expression / Q000187:drug effects*; D006367:HeLa Cells; D006358:Hot Temperature; D006801:Humans; D007535:Isomerases / Q000096:biosynthesis / Q000235:genetics*; D015230:Prostaglandin D2 / Q000494:pharmacology* / Q000031:analogs & derivatives; D019704:Protein Disulfide-Isomerases; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D014415:Tunicamycin / Q000494:pharmacology
D012333:RNA, Messenger; D014415:Tunicamycin; D000001:Calcimycin; C040810:9-deoxy-9,10-didehydro-12,13-didehydro-13,14-dihydroprostaglandin D2; D003513:Cycloheximide; D007535:Isomerases; D019704:Protein Disulfide-Isomerases; D015230:Prostaglandin D2; D004229:Dithiothreitol