Effects of cadmium on telomerase activity, expressions of TERT, c-myc and P53, and apoptosis of rat hepatocytes

Abstract

This study investigated the effect of cadmium on the telomerase activity, the expression of TERT, c-myc and p53 and the apoptosis of rat hepatocytes. The rats were administrated 5, 10 and 20 μmol/kg cadmium chloride intraperitoneally and sacrificed 48 h after the initial treatment. The telomerase activity of the rat hepatocytes was measured by the telomeric repeat amplification protocol (TRAP), and apoptosis was detected by flow cytometry. The mRNA expressions of TERT, c-myc and p53 were measured by reverse transcription-polymerase chain reaction (RT-PCR). C-myc and P53 proteins were determined by immunochemistry. The results showed that cadmium chloride increased the hepatocellular telomerase activity in a dose-dependant manner and induced the apoptosis of hepatocytes significantly. The value of relative coefficient between the telomerase activity and the apoptosis rate was 0.9398. RT-PCR revealed that specific bands corresponding to the TERT mRNA, c-myc mRNA, and p53 mRNA were displayed at 185, 342 and 538 bp respectively. Cadmium chloride could substantially increase the mRNA expressions of TERT, c-myc and p53 in rat hepatocytes, as compared with control. Moreover, cadmium chloride at the doses of 5, 10 and 20 μmol/kg could increase the content of P53 protein in rat hepatocytes obviously, but only that at the doses of 10 and 20 μmol/kg substantially promoted the c-myc protein level in rat hepatocytes. Our study herein suggested that cadmium may contribute to the carcinogenesis by activating telomerase, and overexpressing the mRNAs of TERT, c-myc and p53, and causing apoptosis of normal cells.

Keywords

cadmium / telomerase / apoptosis / telomerase reverse transcriptase / c-myc / p53

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