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Published on: July 3, 2013
Nickel(II)-induced oxidative stress, apoptosis, G2/M arrest, and genotoxicity in normal rat kidney cells
Chang-Yu Chen1, Tsu-Kung Lin, Yi-Chuang Chang
1Department of Medical Technology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
Abstract:
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.
Insights
Nickel chloride (NiCl2) induces oxidative stress and DNA damage in kidney cells. This toxicity involves reactive oxygen species and the Bcl family signaling pathway, leading to renal cell death.
Area of Science:
- Toxicology
- Cell Biology
- Molecular Biology
Background:
- Nickel compounds are environmental pollutants with known toxicity.
- Understanding nickel's impact on renal cells is crucial for public health.
- Oxidative stress and apoptosis are key mechanisms in heavy metal-induced cellular damage.
Purpose of the Study:
- To investigate the effects of nickel chloride (NiCl2) on oxidative stress, apoptosis, and genotoxicity in normal rat kidney (NRK) cells.
- To elucidate the role of reactive oxygen intermediates and Bcl family proteins in nickel-induced renal cytotoxicity.
Main Methods:
- NRK cells were treated with varying concentrations of NiCl2.
- Intracellular oxidants (DCF), lipid peroxidation (TBARS), and DNA damage (comet assay) were measured.
- Flow cytometry was used to analyze cell cycle distribution (sub-G1 phase) and apoptotic protein expression (Bcl-2, Bcl-xL, Bad, Bax).
Main Results:
- NiCl2 treatment increased intracellular oxidants and lipid peroxidation in NRK cells.
- A concentration-dependent increase in sub-G1 phase cells and DNA strand breakage was observed.
- Nickel exposure reduced Bcl-2 and Bcl-xL expression while increasing Bad and Bax expression, indicating apoptosis induction.
Conclusions:
- Nickel chloride induces oxidative stress and genotoxicity in renal cells, potentially through reactive oxygen intermediates.
- The Bcl family-mediated signaling pathway plays a role in nickel-induced renal cytotoxicity.
- These findings highlight the mechanisms of nickel nephrotoxicity.
