15-Deoxy-Delta(12,14)-prostaglandin J2 induces apoptosis through activation of the CHOP gene in HeLa cells.
Cyclopentenone prostaglandins (PGs) of the J series, which are produced by dehydration of PGD(2), have been reported to induce apoptosis in various cell lines. One of these cyclopentenone PGs, 15-deoxy-Delta(12,14)-prostaglandin J(2) (15-d-PGJ(2)), is the most potent inducer of apoptosis in the series, but the signaling pathways by which it induces apoptosis are poorly understood. We recently reported that cyclopentenone PGs accumulate in the endoplasmic reticulum (ER) and it has been shown that the transcription factor CHOP is induced by ER-stresses and elicits apoptosis. In the present study we demonstrated that 15-d-PGJ(2) induces CHOP mRNA/protein in HeLa cells via activation of the conserved regions in the CHOP promoter. Using several mutants of the CHOP promoter fragments, we found that two regions, CCAAT/enhancer-binding protein (C/EBP) site at -313 and ER-stress element (ERSE) at -93, are involved in activation of the CHOP gene by 15-d-PGJ(2). These results suggest that 15-d-PGJ(2) activates the CHOP promoter in two distinct pathways that could induce apoptosis of HeLa cells.
Department of Molecular-Targeting Cancer Prevention, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Japan.
Shoichi
S
Saito
Senye
S
Takahashi
Nobumasa
N
Takagaki
Tohru
T
Hirose
Toshiyuki
T
Sakai
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000502:physiology; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D022762:CCAAT-Enhancer-Binding Proteins; C497249:DDIT3 protein, human; D014157:Transcription Factors; D051742:Transcription Factor CHOP; D015230:Prostaglandin D2