Journal
BIOLOGICAL TRACE ELEMENT RESEARCH
Volume 127, Issue 1, Pages 53-68Publisher
HUMANA PRESS INC
DOI: 10.1007/s12011-008-8223-7
Keywords
Cadmium; Oxidative stress; Apoptosis; Proximal tubular cells; Primary cell culture; Mitochondrial dysfunction; Calcium overload; Intracellular acidification; ATPases
Funding
- National Nature Science Foundation [30440050, 30571364]
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Cadmium (Cd) is a known nephrotoxic element. In this study, the primary cultures of rat proximal tubular (rPT) cells were treated with low doses of cadmium acetate (2.5 and 5 A mu M) to investigate its cytotoxic mechanism. A progressive loss in cell viability, together with a significant increase in the number of apoptotic and necrotic cells, were seen in the experiment. Simultaneously, elevation of intracellular [Ca2+]i and reactive oxygen species (ROS) levels, significant depletion of mitochondrial membrane potential(Delta I) and cellular glutathione (GSH), intracellular acidification, and inhibition of Na+, K+-ATPase and Ca2+-ATPase activities were revealed in a dose-dependent manner during the exposure, while the cellular death and the apoptosis could be markedly reversed by N-acetyl-l-cysteine (NAC). Also, the calcium overload and GSH depletion were significantly affected by NAC. In conclusion, exposure of rPT cells to low-dose cadmium led to cellular death, mediated by an apoptotic and a necrotic mechanism. The apoptotic death might be the chief mechanism, which may be mediated by oxidative stress. Also, a disorder of intracellular homeostasis induced by oxidative stress and mitochondrial dysfunction is a trigger of apoptosis in rPT cells.
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