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Prostaglandin E1 transported into cells blocks the apoptotic signals induced by nerve growth factor deprivation
T Kawamura1, S Horie, T Maruyama
1Osaka Laboratories, Pharmaceutical Research Division, Yoshitomi Pharmaceutical Industries, Ltd., Japan.
Abstract:
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.
Insights
Prostaglandin E1 protects neurons from apoptosis after nerve growth factor deprivation. This neuroprotective effect is mediated by the prostaglandin transporter, which facilitates PGE1 uptake into cells.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Neuronal apoptosis is a critical process in neurodegenerative diseases.
- Nerve growth factor (NGF) deprivation triggers apoptosis in PC12 cells.
- Prostaglandin E1 (PGE1) is a signaling molecule with potential neuroprotective properties.
Purpose of the Study:
- To investigate the role of Prostaglandin E1 (PGE1) in preventing neuronal apoptosis.
- To elucidate the mechanism by which PGE1 exerts its antiapoptotic effects in NGF-deprived PC12 cells.
- To identify the involvement of the prostaglandin transporter in PGE1-mediated neuroprotection.
Main Methods:
- Induction of apoptosis in rat pheochromocytoma PC12 cells via NGF deprivation.
- Assessment of apoptosis using TUNEL staining and chromatin condensation.
- Treatment with Prostaglandin E1 (PGE1) and its effects on cell viability.
- RT-PCR to detect the expression of prostaglandin transporter genes.
- Inhibition of prostaglandin transporter using Bromcresol green and antisense oligonucleotides.
- Measurement of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) activity.
Main Results:
- NGF deprivation induced neuronal apoptosis in PC12 cells within 8 hours.
- PGE1 significantly reduced the incidence of apoptotic cell death.
- Prostaglandin transporter genes were expressed in PC12 cells.
- Inhibition of the prostaglandin transporter blocked the antiapoptotic effect of PGE1.
- PGE1 counteracted the activation of SAPK/JNK signaling pathways.
Conclusions:
- PGE1 exhibits significant antiapoptotic effects in NGF-deprived PC12 cells.
- The prostaglandin transporter plays a crucial role in mediating the neuroprotective actions of PGE1.
- PGE1-induced neuroprotection involves the inhibition of SAPK/JNK signaling following transporter-mediated uptake.