Odani N, Negishi M, Takahashi S, Ichikawa A
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Biochem Biophys Res Commun. 1996 Mar 18;220(2):264-8. doi: 10.1006/bbrc.1996.0393.
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.
蛋白质二硫键异构酶（PDI）催化正确的蛋白质二硫键形成，是蛋白质折叠的关键调节因子。我们研究了硫醇反应性应激前列腺素δ12-前列腺素（PG）J2对PDI基因表达的影响。δ12-PGJ2可瞬时诱导HeLa细胞中的PDI mRNA。其他导致未折叠蛋白积累的应激诱导剂，如衣霉素、A23187和热休克，也可诱导PDI mRNA，表明未折叠蛋白积累反应可诱导PDI基因表达。环己酰亚胺本身可强烈诱导PDI mRNA，但不抑制δ12-PGJ2的作用，这表明δ12-PGJ2诱导PDI基因表达的途径不涉及未折叠蛋白的积累。另一方面，还原剂二硫苏糖醇可诱导PDI mRNA，而δ12-PGJ2并未产生累加诱导作用。因此，δ12-PGJ2通过一条独立于从头蛋白质合成的途径诱导PDI基因表达。
