Mice liver protein synthesis in vivo and in vitro after cadmium chloride administration

Abstract

Objective: To evaluate effects of cadmium ions on the protein synthesis in mice liver in vivo and in vitro. Methods: Experiments were done on white laboratory mice using i.p. injections of appropriate amounts of cadmium chloride solution. Protein synthesis or tRNA acceptor activity was evaluated by the incorporation of [ 14 C]-leucine into newly synthesized peptides and proteins or formation of aminoacyl-tRNA. Liver cell-free translation system was made on the basis of post-mitochondrial supernatant. Results: Single doses of Cd 2+ at the amounts equal to 0.025 LD 50 and 0.05 LD 50 (0.08 mg/kg and 0.16 mg/kg) do not have very significant impact on the protein synthesis in liver 24 h after the heavy metal administration. Only 0.5 LD 50 Cd 2+ (1.6 mg/kg) reduces protein synthesis by approximately one third. However, within 24 h after the intoxication with 0.5 LD 50 , cadmium revealed initial inhibition of translation within the first 2 - 4 h, which progressed into stimulation, reaching its maximum at the 8th h and subsequent decrease. In vitro cadmium at lower concentration (40 μM) demonstrated stimulatory effect on both measured parameters of translation -the rate and level, while sharp inhibition of protein synthesis began only at relatively high concentration of this heavy metal (above 60 pM). When treated in vivo, 0.5 LD 50 cadmium 2 h after injection reduced the acceptor activity of tRNA almost by 50%, but already 8 h after the injection acceptor activity of tRNA was back at the level of control. Cadmium chloride when added directly to the liver extracts of control animals displayed very strong inhibitory effect on the tRNA acceptor activity, which had linear dependence on the cadmium concentration. Conclusions: Cadmium induces significant fluctuations of liver protein synthesis at the early stages of intoxication in vivo, which includes both inhibition and stimulation. Cadmium significantly reduces the acceptor activity of liver tRNA both in vivo and in vitro.