Localization of a cyclopentenone prostaglandin to the endoplasmic reticulum and induction of BiP mRNA.
Cyclopentenone prostaglandins (PGs) are transported into cells and stimulate 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 fluorescent probe, pyrene, into two types of PG analogue, GIF0010 (a cyclopentenone type) and GIF0037 (a cyclopentanone type) and examined their intracellular 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 reticulum (ER) and markedly induced BiP gene expression. By contrast, GIF0037 and pyrene neither accumulated in the cell nor induced BiP gene expression. Thus the ER localization of GIF0010 and the induction of gene expression by GIF0010 are ascribed to the cyclopentenone structure. Treatment with cycloheximide inhibited both the accumulation of GIF0010 and the induction of the BiP mRNA, suggesting that the ER localization of the PG and subsequent gene expression require the nascent protein synthesis. These results demonstrate that the cyclopentenone PG is specifically accumulated in the ER, transducing a signal for BiP gene expression in the nuclei.
Takahashi
S
S
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Odani
N
N
Tomokiyo
K
K
Furuta
K
K
Suzuki
M
M
Ichikawa
A
A
Negishi
M
M
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics*; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005456:Fluorescent Dyes / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis* / Q000235:genetics*; D018832:Molecular Chaperones / Q000096:biosynthesis* / Q000235:genetics*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D011465:Prostaglandins, Synthetic / Q000494:pharmacology*; D017510:Protein Folding; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011721:Pyrenes / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats
D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D005456:Fluorescent Dyes; C115325:GIF 0010; C115326:GIF 0037; D006360:Heat-Shock Proteins; D007143:Immunoglobulin Heavy Chains; D018832:Molecular Chaperones; D011465:Prostaglandins, Synthetic; D011500:Protein Synthesis Inhibitors; D011721:Pyrenes; D012333:RNA, Messenger; C037112:9-deoxy-delta-9-prostaglandin D2; D004247:DNA; D003513:Cycloheximide; C030984:pyrene; D015230:Prostaglandin D2