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

被引:31
作者
Cho, MK [1 ]
Kim, YG [1 ]
Lee, MG [1 ]
Kim, SG [1 ]
机构
[1] Seoul Natl Univ, Coll Pharm, Kwanak Gu, Seoul 151742, South Korea
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2000年 / 1502卷 / 02期
基金
新加坡国家研究基金会;
关键词
protein-calorie malnutrition; Nrf-1/2; cysteine; methionine; glutathione S-transferase; antioxidant response element;
D O I
10.1016/S0925-4439(00)00046-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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% and 70% suppressed. Increased GSTA3/5 expression was significantly prevented by cysteine or methionine treatment, although such treatment failed to restore the rGSTM2 level. In contrast to differential GST protein expression, PCM 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 completely abolished by cysteine or methionine treatment during PCM, although the rGSTM2 mRNA level was not restored. PCM induced oxidative stress in the liver, as evidenced by protein carbonylation. Antioxidant response element (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 GSTs were differentially expressed during PCM, that certain GST mRNAs were increased with the ARE activation, and that cysteine was active in preventing increases in GST mRNAs and ARE activation. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:235 / 246
页数:12
相关论文
共 42 条
[1]  
Amato SF, 1998, CANCER RES, V58, P241
[2]  
BERGELSON S, 1994, ONCOGENE, V9, P565
[3]   Oxygen sensing and molecular adaptation to hypoxia [J].
Bunn, HF ;
Poyton, RO .
PHYSIOLOGICAL REVIEWS, 1996, 76 (03) :839-885
[4]   INFLUENCE OF PROTEIN NUTRITION ON PROTEOLYTIC ACTIVITY AND HISTONE CONTENT IN ISOLATED MOUSE-LIVER NUCLEI [J].
CASSIA, RO ;
CONDE, RD .
HORMONE AND METABOLIC RESEARCH, 1994, 26 (03) :137-140
[5]   Suppression of rat hepatic cytochrome P450s by protein-calorie malnutrition: Complete or partial restoration by cysteine or methionine supplementation [J].
Cho, MK ;
Kim, YG ;
Lee, MG ;
Kim, SG .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1999, 372 (01) :150-158
[6]   THERAPEUTIC EFFECTIVENESS OF CYSTAMINE AND CYSTEINE TO REDUCE LIVER-CELL NECROSIS INDUCED BY SEVERAL HEPATOTOXINS [J].
DEFERREYRA, EC ;
DEFENOS, OM ;
BERNACCHI, AS ;
DECASTRO, CR ;
CASTRO, JA .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1979, 48 (02) :221-228
[7]   Signal transduction - A bridge to control [J].
Demple, B .
SCIENCE, 1998, 279 (5357) :1655-1656
[9]   Contribution of breakdown in the regulation of mouse liver glutathione S-transferase subunits during protein depletion and re-feeding [J].
García-Mata, R ;
Conde, RD ;
Sanllorenti, PM .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 1998, 1448 (01) :46-50
[10]   EFFECT OF DIETARY LEVEL OF PROTEIN ON THE ACTIVITY OF MOUSE-LIVER CALPAIN [J].
GOICOECHEA, SM ;
TABARES, ML ;
SABAS, ME ;
PUCCIARELLI, MG ;
CONDE, RD .
HORMONE AND METABOLIC RESEARCH, 1994, 26 (04) :175-180