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Journal of Korean Neurosurgical Society 1998;27(11): 1475-1480.
Underlying Mechanism of Cisplatin-induced Apoptosis in PC-12 Cells.
Young Woo Lee, Sae Ock Oh, Won Ho Cho, Sang Ho Lee
1Department of Neurosurgery, College of Medicine, Pusan National University, Pusan, Korea.
2Department of Physiology, College of Medicine, Pusan National University, Pusan, Korea.
Cisplatin is a widely used antitumor drug of which the dose-limiting toxicity is predominantly large-fiber neuropathy. Cisplatin-induced neurotoxicity includes sensory and autonomic neurotoxicity of which the mechanism has not been clarified. To determine whether cisplatin induces apoptosis of neuron and to investigate the mechanism of the apoptosis, we observe the effect of cisplatin on the rat pheochromocytoma cells(PC-12 cells). Apoptosis of PC-12 cells was induced dose-and time-dependently by the treatment of cisplatin. Cisplatininduced apoptosis of PC-12 cells was identified by DNA fragmentation. During cisplatin-induced apoptosis of PC-12 cells stress-activated protein kinase(SAPK) activity was increased and mitogen-activated protein kinase(MAPK) activity was decreased. The expression of Bcl-2 was decreased by the treatment of cisplatin without effect on the expression of other Bcl-2 related proteins. It is speculated that cisplatin may induce apoptosis in PC-12 cells by regulation of Bcl-2 related proteins and this regulation might be associated with activation of SAPK and inhibition of MAPK.
Key Words: Cisplatin; Apoptosis; PC-12 cells
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