Prostaglandin E1 Transported into Cells Blocks the Apoptotic Signals Induced by Nerve Growth Factor Deprivation

• Published in: Journal of neurochemistry 1999-05, Vol.72 (5), p.1907-1914
• Main Authors: Kawamura, Tom, Horie, Satoshi, Maruyama, Tomoyuki, Akira, Toshiaki, Imagawa, Takashi, Nakamura, Norifumi
• Format: Article
• Language: English
• Subjects: Ageing, cell death; Alprostadil - pharmacokinetics; Alprostadil - pharmacology; Animals; Antiporters - metabolism; Antiporters - physiology; Apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Biological and medical sciences; Biological Transport - physiology; Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors; Cell Differentiation - physiology; Cell physiology; Cyclic AMP - metabolism; DNA-Binding Proteins - metabolism; DNA-Binding Proteins - physiology; Fundamental and applied biological sciences. Psychology; Intracellular Membranes - physiology; Molecular and cellular biology; Nerve growth factor deprivation; Nerve Growth Factors - deficiency; Nerve Growth Factors - pharmacology; Neurons - drug effects; Neurons - metabolism; Neurons - physiology; Organic Anion Transporters; PC12 cells; PC12 Cells - drug effects; PC12 Cells - metabolism; PC12 Cells - pathology; Prostaglandin E1; Prostaglandin transporter; Rats; Signal Transduction - drug effects; Signal Transduction - physiology
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1999.0721907.x

: 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 (10−7‐10−6M) reduced the incidence of apoptotic cell death in PC12 cells. The genes encoding PG transporter specific to prostaglandins such as PGE2 or PGF2α 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/c‐Jun 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.