Nickel(II)-induced oxidative stress, apoptosis, G2/M arrest, and genotoxicity in normal rat kidney cells.
In order to elucidate the effects of nickel (Ni) on oxidative stress, apoptosis, and genotoxicity in renal cells, the levels of intracellular oxidants, lipid peroxidation, apoptotic proteins, and DNA damage were measured in normal rat kidney (NRK) cells after nickel chloride (NiCl(2)) treatment. NiCl(2) appeared to increase the formation of the fluorescent oxidized compound (dichlorofluorescein, DCF) and levels of thiobarbituric acid-reactive substances (TBARS). In flow cytometric analysis, a rise in cell proportion in sub-G1 phase occurred in a concentration-dependent manner. After Ni treatment, there was reduced expression of Bcl-2 and Bcl-xL proteins, while induced Bad and Bax proteins expression was higher. Single-strand DNA breakage induced by Ni in NRK cells was determined by comet assay. Significant increase DNA damage score (arbitrary units) was noted in a concentration-related manner after treatment with Ni. Induction of intracellular oxidants by Ni was accompanied by an increasing frequency of DNA strand breakage. Our data indicate that Ni-induced oxidative stress and genotoxicity in NRK cells may involve reactive oxygen intermediates, and that Bcl family-mediated signaling pathway may be involved in positive regulation of Ni-induced renal cytotoxicity.
Chen
Chang-Yu
CY
Department of Medical Technology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Lin
Tsu-Kung
TK
Chang
Yi-Chuang
YC
Wang
Yi-Fen
YF
Shyu
Huey-Wen
HW
Lin
Kuan-Hua
KH
Chou
Miao-Chen
MC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020552:Comet Assay; D004249:DNA Damage; D016195:G2 Phase / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D009153:Mutagens / Q000633:toxicity*; D009532:Nickel / Q000633:toxicity*; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats
D009153:Mutagens; D016877:Oxidants; D019253:Proto-Oncogene Proteins c-bcl-2; C022838:nickel chloride; D009532:Nickel