The effect of cysteine on the altered expression of class alpha and mu glutathione S-transferase genes in the rat liver during protein-calorie malnutrition

Citation
Mk. Cho et al., The effect of cysteine on the altered expression of class alpha and mu glutathione S-transferase genes in the rat liver during protein-calorie malnutrition, BBA-MOL BAS, 1502(2), 2000, pp. 235-246
Citations number
42
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medical Research General Topics
Journal title
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
ISSN journal
0925-4439 → ACNP
Volume
1502
Issue
2
Year of publication
2000
Pages
235 - 246
Database
ISI
SICI code
0925-4439(20001018)1502:2<235:TEOCOT>2.0.ZU;2-M
Abstract
Protein-calorie malnutrition (PCM) represents a global health problem. The breakdown rate of glutathione S-transferase (GST) subunits determines their differential contents during protein depletion. Hepatic GST expression and the underlying mechanistic basis were investigated in PCM rats. PCM caused no change in rGSTA1/2 subunit. In contrast, rGSTA3/5 subunit was 2.4-fold induced during PCM, while the levels for rGSTM1 and M2 subunits were 30% an d 70% suppressed. Increased GSTA3/5 expression was significantly prevented by cysteine or methionine treatment, although such treatment failed to rest ore the rGSTM2 level. In contrast to differential GST protein expression, P CM caused a 5-10-fold increase in rGSTA2/A3/A5 and MI mRNAs, whereas rGSTM2 mRNA was 70% decreased. The elevations in rGSTA2/A3/A5 and M1 mRNAs were c ompletely abolished by cysteine or methionine treatment during PCM, althoug h the rGSTM2 mRNA level was not restored. PCM induced oxidative stress in t he liver, as evidenced by protein carbonylation. Antioxidant response eleme nt (ARE)-binding activity of nuclear extracts from PCM rats was increased, which was immunodepleted with anti-Nrf1/2 antibodies. Activation of nuclear ARE-binding proteins was inhibited by cysteine. Data showed that hepatic G STs were differentially expressed during PCM, that certain GST mRNAs were i ncreased with the ARE activation, and that cysteine was active in preventin g increases in GST mRNAs and ARE activation. (C) 2000 Elsevier Science B.V. All rights reserved.