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

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% 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.

Oxidative stress in mouse liver caused by dietary amino acid deprivation: protective effect of methionine

“…A common feature among these enzymes is their link with the redox status of cell. In addition, similarly to low-protein diets [12,24], we report here that feeding with PFD decreases hepatic GSH content. These changes explain the increased hepatic ROS content, which led to protein oxidation.…”

“…It has been shown that malnutrition causes oxidative stress in liver [12,13,31,40,51]. We report here that PFD decreases the content of mouse liver CAT, GPx and Prx-I.…”

Protective Effects of Zinc on Oxidative Stress Enzymes in Liver of Protein-Deficient Rats

“…Ramdath and Golden 58 reported a similar increase in malnourished children. Cho et al 59 stated that the antioxidant response element (ARE)-binding activity of protein-calorie malnutrition rats gets increased, which in turn results in activation of certain GST mRNAs and a higher GST activity.…”

Methionine restriction up‐regulates the expression of the pi class of glutathione S‐transferase partially via the extracellular signal‐regulated kinase‐activator protein‐1 signaling pathway initiated by glutathione depletion

“…For instance, mouse liver contents of the GSTA3 and GSTP1 were increased with a protein-free diet, whereas normal contents were preserved with a protein-free diet replenished with either L-methionine or L-cysteine [20]. Moreover, mRNA levels of GSTA2/3/5 and GSTM1 in rat livers were increased by protein-calorie restriction, and this increase could be normalized by supplementation with L-cysteine or L-methionine [21].…”