Oct 13, 2001

Cisplatin-induced apoptosis by translocation of endogenous Bax in mouse collecting duct cells

Biochemical Pharmacology
R H LeeJ S Jung

Abstract

cis-platinum(II) (cis-diammine dichloroplatinum; cisplatin) is a potent antitumor compound that is widely used for the treatment of many malignancies. An important side-effect of cisplatin is nephrotoxicity, which results from injury to renal tubular epithelial cells and can be manifested as either acute renal failure or a chronic syndrome characterized by renal electrolyte wasting. Recently, apoptosis has been recognized as an important mechanism of cell death mediating the antitumor effect of cisplatin. This study was undertaken to examine the mechanisms of cell death induced by cisplatin in M-1 cells, which were derived from the outer cortical collecting duct cells of SV40 transgenic mice. Treatment of M-1 cells with high concentrations of cisplatin (0.5 and 1 mM) for 2 hr led to necrotic cell death, whereas a 24-hr treatment with 5-20 microM cisplatin led to apoptosis. Antioxidants protected against cisplatin-induced necrosis, but not apoptosis, indicating that reactive oxygen species play a role in mediating necrosis but not apoptosis induced by cisplatin and that the mechanism of cell death induced by cisplatin is concentration dependent. The low concentrations of cisplatin, which induced apoptosis in M-1 cells, did not a...Continue Reading

  • References48
  • Citations71

References

Mentioned in this Paper

Wasting
JUN gene
Mechanism of Cell Death
Necrosis
Antineoplastic Agents
Electrolytes
Kidney - Cortex - Renal Tubule - Collecting Duct (Mmhcc)
Apoptosis, Intrinsic Pathway
Mitogen-Activated Protein Kinases
Kidney Failure, Acute

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