Prostaglandin E1 transported into cells blocks the apoptotic signals induced by nerve growth factor deprivation.
Neuronal apoptosis in rat pheochromocytoma PC12 cells, which was confirmed by TUNEL (terminal transferase-mediated dUTP-biotin nick end-labeling) staining and detection of chromatin condensation, appeared within 8 h after nerve growth factor (NGF) deprivation. Prostaglandin (PG) E1 (10(-7)-10(6) M) reduced the incidence of apoptotic cell death in PC12 cells. The genes encoding PG transporter specific to prostaglandins such as PGE2 or PGF2alpha were expressed in the cell lines as shown by RT-PCR. Bromcresol green, an inhibitor of PG transporter, reversed the antiapoptotic effect of PGE1. Moreover, treatment of PC12 cells with an antisense oligonucleotide corresponding to PG transporter cDNA also blocked the inhibitory effects of PGE1 on apoptotic cell death. In addition, PGE1 counteracted the increased activities of stress-activated protein kinase/cJun N-terminal kinase within 1-2 h after NGF deprivation in PC12 cells. These results indicated that the antiapoptotic effect of PGE1 in NGF-deprived PC12 cells was achieved by inhibitory signals following uptake into neurons through the PG transporter.
Kawamura
T
T
Osaka Laboratories, Pharmaceutical Research Division, Yoshitomi Pharmaceutical Industries, Ltd., Japan.
Horie
S
S
Maruyama
T
T
Akira
T
T
Imagawa
T
T
Nakamura
N
N
D000527:Alprostadil / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D017920:Antiporters / Q000378:metabolism / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001692:Biological Transport / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D002454:Cell Differentiation / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D007425:Intracellular Membranes / Q000502:physiology; D009414:Nerve Growth Factors / Q000172:deficiency* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D027361:Organic Anion Transporters; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D017920:Antiporters; D004268:DNA-Binding Proteins; D009414:Nerve Growth Factors; D027361:Organic Anion Transporters; C503528:Slco2a1 protein, rat; D000242:Cyclic AMP; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000527:Alprostadil