Cadmium chloride-induced apoptosis of HK-2 cells via interfering with mitochondrial respiratory chain.

Cadmium could induce cell apoptosis, probably related to the dysfunction of the mitochondrial respiratory chain. The human renal proximal tubule (HK-2) was used to explore the mechanism of mitochondrial respiratory chain dysfunction during apoptosis induced by cadmium chloride (CdCl). Cell viability was evaluated by cell proliferation assay and different concentrations of 60, 80 and 100 μM were selected to evaluate the mitochondrial toxicity of CdCl respectively. Under the CdCl treatment for 24 h, the mitochondrial reactive oxygen species (ROS) of HK-2 cells increased and the superoxide dismutase (SOD) activity was inhibited at the above three concentrations separately. Both ATP content and mitochondrial membrane potential decreased significantly at 100 μM concentration. The levels of procaspase-3 and Bcl-2 had fallen in a concentration-dependent manner and Bax was significantly increased at 60, 80 and 100 μM concentration compared with no CdCl treatment respectively, which activated the mitochondrial apoptosis pathway. N-acetyl-cysteine (NAC) could partially resist CdCl-induced cell apoptosis, while myxothiazol (Myx) promoted the process. Mitochondria relative alterations manifested as inhibition of complex III and V. In addition, both the quantity of mitochondrial coenzyme Q-binding protein CoQ10 homolog B (CoQ10B) and cytochrome c (Cyt c) had decreased significantly. Taken together, CdCl induced HK-2 apoptosis due to the mitochondrial respiratory chain dysfunction by reducing the CoQ10B level, offering a novel evaluating indicator for the environmental toxicity of CdCl.