Relationship between expression of HSP70 and metallothionein and oxidative stress during mercury chloride induced acute liver injury in rats.
Mercury is a highly toxic metal which induces oxidative stress. Metallothionein and heat shock protein 70 (HSP70) are stress proteins involved in response to different stimuli. In the present study rats were administered per oral application by gavage, a single daily dose (0.1 mg/kg) of HgCl(2) for 3 consecutive days. To find a relation between these two stress proteins and mercury, parameters of liver injury, redox state of the cells, and the expression and protein levels of HSP70 and metallothionein by Northern and Western blot analysis were assayed either in blood or in liver. HgCl(2) at the doses of 0.1 mg/kg induced liver injury detected by a slight increase in serum aspartate aminotransferase and alkaline phosphatase activities and by the enhanced levels of bilirubin. Oxidative stress was detected by a significant decrease in protein-SH and an increase in thiobarbituric acid reactive substances in liver following one dose of mercury. mRNA and protein levels of both metallothionein and HSP70 increased progressively from first to third doses of mercury. We conclude that against low doses of mercury that produce a slight liver injury and oxidative stress, the liver rapidly responds by inducing the expression of metallothionein and HSP70. We suggest that metallothionein induction attenuates the decrease in protein-SH induced by the first dose of mercury, since metallothionein increases the pool of thiol groups in the cytosol eliminating oxygen radicals and inhibiting lipid peroxidation. From these results we can suggest that the changes observed in these stress proteins by the effect of mercury appear to be a response rapidly induced at transcriptional and at translational levels.
Reus
Isabel Sánchez
IS
Instituto de Bioquímica (CSIC-UCM), Facultad de Farmacia, Universidad Complutense, Plaza de Ramón y Cajal sn, 28040 Madrid, Spain.
Bando
Inmaculada
I
Andrés
David
D
Cascales
María
M
D000818:Animals; D015152:Blotting, Northern; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity*; D008668:Metallothionein / Q000096:biosynthesis*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D008627:Mercuric Chloride; D008668:Metallothionein