Subacute effects of cadmium and zinc ions on protein synthesis and cell death in mouse liver

Inga Stanevičienė, Ilona Sadauskienė, Vaiva Lesauskaitė¹, Laima Ivanovienė², Artūras Kašauskas², Leonid Ivanov

Laboratory of Pathochemistry, Institute for Biomedical Research, ¹Institute of Cardiology, ²Department of Biochemistry, Kaunas University of Medicine, Lithuania

Key words: cadmium; zinc; protein synthesis; apoptosis; mouse liver.

Summary. Objective. The aim of this study was to evaluate in vivo the effects of cadmium and zinc ions on translational machinery and death of mouse liver cells.

Material and methods. Outbred mice received intraperitoneal injections of cadmium chloride solution (1.4 µmoles cadmium per 1 kg of body weight) and/or zinc sulfate solution (4.8 µmoles zinc per kg of body weight) three times per week for six weeks. Analogical volume of saline solution was injected to the control mice. Protein synthesis was evaluated by incorporation of [¹⁴C]-labeled leucine into peptides and proteins. Total tRNAs were isolated using deproteinized extract of liver tissue. Postmitochondrial supernatant was as a source of leucyl-tRNA synthetase. Activities of tRNA^Leu and leucyl-tRNA synthetase were measured by an aminoacylation reaction using [¹⁴C]-labeled leucine. Liver cell apoptosis was detected by TUNEL assay using in situ cell death detection kit.

Results. A decrease in incorporation of [¹⁴C]-labeled leucine into proteins was detected in liver, kidney, and heart as well as diminution of tRNA^Leu acceptor activity in cadmium-exposed liver. Cadmium caused activation of the leucyl-tRNA synthetase and induced liver cell apoptosis. Pretreatment of mice with zinc sulfate solution favored to protection of protein synthesis and acceptor activity of tRNALeu against cadmium-induced inhibition. Under co-exposure of mouse liver to cadmium and zinc, activity of the leucyl-tRNA synthetase was at the level of control. Zinc did not influence TUNEL-positive cell number in cadmium-exposed mouse liver.

Conclusions. Under subacute intoxication of mice by cadmium, zinc ions protect the translation machinery against inhibition, but do not decrease the number of apoptotic cells in the liver.

Correspondence to I. Stanevičienė, Laboratory of Pathochemistry, Institute for Biomedical Research, Kaunas University of Medicine, Eivenių 4, 50009 Kaunas, Lithuania. E-mail: ingija@med.kmu.lt

Received 22 November 2007, accepted 1 February 2008