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.
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 M1 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-Nrf-1/2 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.
Cho
M K
MK
College of Pharmacy, Seoul National University, Sillim-dong, Kwanak-gu, 151-742, Seoul, South Korea.
Kim
Y G
YG
Lee
M G
MG
Kim
S G
SG
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001483:Base Sequence; D002352:Carrier Proteins / Q000378:metabolism; D003545:Cysteine / Q000097:blood / Q000494:pharmacology*; D003553:Cystine / Q000097:blood; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000145:classification / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D011502:Protein-Energy Malnutrition / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D002352:Carrier Proteins; D017931:DNA Primers; D007527:Isoenzymes; D012333:RNA, Messenger; D003553:Cystine; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha; D005978:Glutathione; D003545:Cysteine