title: [Mechanisms of nephrotoxicity of novel anticancer compound maleimide derivative MI-1].
abstract: The features of the impact of the maleimide derivative 1-(4-Cl-benzyl)-3-chloro-4-(CF3-fenilamino)-1H-pyrrole-2,5-dione (MI-1) on the viability and apoptosis-induced cell death of renal proximal and distal tubular epithelial cells and the amount of total and phosphorylated ERK1/2 were studied in order to establish possible mechanisms of nephrotoxicity induced by of MI-1. The viability and apoptosis of renal epithelial tubular cells after incubation with MI-1 were perfomed by 3,4,5-dymetyltiazol-2-yl-2,5-diphenyl-tetrazolium bromide (MTT)-test and by flow cytometry after staining with specific antibodies to annexin V, respectively. The amount of ERK 1/2 was determined by Western blotting. The data indicate that MI-1 was more toxic with respect to the epithelial cells of distal than proximal tubule cells. The apoptosis-induced cell death pathway is involved in the mechanisms of MI-1 cytotoxicity. One of the possible mechanisms of MI-1 nephrotoxicity is increase in phosphorylation of ERK1/2 in the distal tubules. At the same time the increase amount of total ERK1/2 in proximal tubules under the influence of MI-1 may contribute to the survival of proximal tubular epithelial cells under the impact of a toxic factor or oxidative stress.
authors: I V
authors: IV
authors: Kharchuk
authors: O O
authors: OO
authors: Andrukhova
authors: V K
authors: VK
authors: Rybal'chenko
authors: O
authors: O
authors: Andrukhov
mesh_terms: D000818:Animals; D017304:Annexin A5; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008301:Maleimides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects
chemical_list: C550019:1-(4-Cl-benzyl)-3-Cl-4-(CF3-phenylamino)-1H-pyrrol-2.5-dione; D017304:Annexin A5; D000970:Antineoplastic Agents; D008301:Maleimides; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3