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


METHODS
Outbred mice received intraperitoneal injections of cadmium chloride solution (1.4 micromoles cadmium per 1 kg of body weight) and/or zinc sulfate solution (4.8 micromoles 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 [(14)C]-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 [(14)C]-labeled leucine. Liver cell apoptosis was detected by TUNEL assay using in situ cell death detection kit.


RESULTS
A decrease in incorporation of [(14)C]-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 tRNA(Leu) 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.
Staneviciene
Inga
I
Laboratory of Pathochemistry, Institute for Biomedical Research, Kaunas University of Medicine, Eiveniu 4, 50009 Kaunas, Lithuania. ingija@med.kmu.lt
Sadauskiene
Ilona
I
Lesauskaite
Vaiva
V
Ivanoviene
Laima
L
Kasauskas
Artūras
A
Ivanov
Leonid
L
D000604:Amino Acyl-tRNA Synthetases / Q000378:metabolism; D032761:Animal Experimentation; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000633:toxicity*; D002105:Cadmium Poisoning / Q000378:metabolism*; D002250:Carbon Radioisotopes; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D007935:Leucine-tRNA Ligase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D014176:Protein Biosynthesis / Q000187:drug effects* / Q000235:genetics; D012343:RNA, Transfer / Q000378:metabolism; D012996:Solutions; D013997:Time Factors; D046249:Transfer RNA Aminoacylation; D019287:Zinc Sulfate / Q000008:administration & dosage / Q000494:pharmacology*
D002250:Carbon Radioisotopes; D012996:Solutions; D019287:Zinc Sulfate; D012343:RNA, Transfer; D000604:Amino Acyl-tRNA Synthetases; D007935:Leucine-tRNA Ligase; D019256:Cadmium Chloride