Role of oxidative stress, apoptosis, and intracellular homeostasis in primary cultures of rat proximal tubular cells exposed to cadmium.
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 microM) 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 [Ca(2+)]i and reactive oxygen species (ROS) levels, significant depletion of mitochondrial membrane potential(Delta Psi) and cellular glutathione (GSH), intracellular acidification, and inhibition of Na(+), K(+)-ATPase and Ca(2+)-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.
Wang
Lin
L
College of Veterinary Medicine, Yangzhou University, 12 East Wenhui Road, Yangzhou, 225009, People's Republic of China.
Cao
Jin
J
Chen
Dawei
D
Liu
Xuezhong
X
Lu
Hao
H
Liu
Zongping
Z
D000085:Acetates / Q000633:toxicity*; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D000085:Acetates; D017382:Reactive Oxygen Species; D002104:Cadmium; C028031:cadmium acetate; D000251:Adenosine Triphosphatases; C034688:sodium calcium ATPase; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione; D002118:Calcium