Rat HMGCoA reductase activation in thioacetamide-induced liver injury is related to an increased reactive oxygen species content.
OBJECTIVE
In thioacetamide-induced liver injury a modification of isoprenoid content and an increase of reactive oxygen species has been described. We have examined how reactive oxygen species influence the 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate limiting enzyme of the isoprenoid biosynthetic pathway, to verify if changes of that enzyme activity are involved in the changed lipid composition of the liver.


METHODS
In chronic and acute thioacetamide-treated rat liver we measured the reactive oxygen species content, the activation state and K(M), the level and degradation rate of the hepatic reductase, its short term regulatory enzymes and the liver lipid profile.


RESULTS
In thioacetamide-treated rat liver, the reactive oxygen species content is high and the reductase is fully activated with no modifications in its K(M) and its short term regulatory enzymes. The reductase level is reduced in chronic thioacetamide treated rats and its degradation rate is altered.


CONCLUSIONS
The data show a relationship between reactive oxygen species production and altered 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. It is suggested that reducing the levels of reactive oxygen species may improve the altered lipid profile found in liver injury.
Pallottini
Valentina
V
Department of Biology, University of Rome Roma Tre, Viale Marconi 446, 00146-Rome, Italy. vpallott@uniroma3.it
Martini
Chiara
C
Bassi
Anna M
AM
Romano
Paola
P
Nanni
Giorgio
G
Trentalance
Anna
A
D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D006903:Hydroxymethylglutaryl CoA Reductases / Q000187:drug effects / Q000378:metabolism*; D017093:Liver Failure / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013853:Thioacetamide / Q000633:toxicity
D017382:Reactive Oxygen Species; D013853:Thioacetamide; D006903:Hydroxymethylglutaryl CoA Reductases