LOCALIZATION OF A CYCLOPENTENONE PROSTAGLANDIN TO THE ENDOPLASMIC-RETICULUM AND INDUCTION OF BIP MESSENGER-RNA

Cyclopentenone prostaglandins (PGs) are transported into cells and sti mulate the expression of various stress genes, such as that coding for BiP (an ER luminal protein). To reveal the site of action of the PGs for the induction of stress-gene expression, we introduced a fluoresce nt probe, pyrene, into two types of PG analogue, GIF0010 (a cyclopente none type) and GIF0037 (a cyclopentanone type) and examined their intr acellular localization in normal rat kidney cells and their ability to induce the BiP gene expression. GIF0010 accumulated around the nuclei and coincided with BiP, a resident protein in the endoplasmic reticul um (ER) and markedly induced BiP gene expression. By contrast, GIF0037 and pyrene neither accumulated in the cell nor induced BiP gene expre ssion. Thus the ER localization of GIF0010 and the induction of gene e xpression by GIF0010 are ascribed to the cyclopentenone structure. Tre atment with cycloheximide inhibited both the accumulation of GIF0010 a nd the induction of the BiP mRNA, suggesting that the ER localization of the PG and subsequent gene expression require the nascent protein s ynthesis. These results demonstrate that the cyclopentenone PG is spec ifically accumulated in the ER, transducing a signal for BiP gene expr ession in the nuclei.