کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2596599 1132537 2010 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cellular and molecular mechanisms of bromate-induced cytotoxicity in human and rat kidney cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Cellular and molecular mechanisms of bromate-induced cytotoxicity in human and rat kidney cells
چکیده انگلیسی
The mechanisms of bromate (BrO3−)-induced toxicity in Normal Rat Kidney (NRK) and human embryonic kidney 293 (HEK293) cells were investigated. BrO3− (added as KBrO3) induced concentration-dependent decreases in 3-(4, dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) staining after 48 h. BrO3−-induced necrosis based on tandem increases in annexin V and PI staining. Cell cycle analysis demonstrated that BrO3− also induced G2/M arrest and nuclear fragmentation, prior to alterations in MTT staining or annexin V and PI staining. Immunoblot analysis demonstrated that the G2/M arrest correlated to induction of phosphorylated (p)-p53, p21, cyclin B1 and p-cdc2. Further, BrO3− induced time-dependent increases in the activity of the mitogen activated protein kinases p38 and ERK1/2. Treatment of cells with the p38 inhibitor SB202190, but not the ERK1/2 inhibitor PD98059, partially reversed BrO3−-induced G2/M arrest and decreased BrO3−-induced p-p53, p21 and cyclin B1 expression. In addition, BrO3− treatment induced reactive oxygen species (ROS) based on increases in CM-H2DCFDA fluorescence. The antioxidant ascorbic acid inhibited BrO3−-induced p38 activation, G2/M arrest, p-p53, p21 and cyclin B1 expression; however, ascorbic acid had no effect on BrO3−-induced formation of 8-OHdG, a marker of DNA oxidative damage, whose increases preceded cell death by 24 h. These data suggest that ROS mediated MAPK activation is involved in the molecular mechanisms of BrO3−-induced cell cycle arrest, which occurs independently of 8-OH-dG production. The similar mode of action in both NRK and HEK293 cells suggests that the mechanisms of BrO3−-induced renal cell death are model-independent.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 269, Issue 1, 28 February 2010, Pages 13-23
نویسندگان
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