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Glutathione transferases (GSTs) are generally recognized for their role in phase II detoxification reactions. However, it is becoming increasingly apparent that members of the GST family also have a diverse range of other functions that are, in general, unrelated to detoxification. One such action is a specific inhibition of the cardiac isoform of the ryanodine receptor (RyR2) intracellular Ca(2+) release channel. In this review, we compare functional and physical interactions between members of the GST family, including GSTO1-1, GSTA1-1, and GSTM2-2, with RyR2 and with the skeletal isoform of the ryanodine receptor (RyR1). The active part of the muscle-specific GSTM2-2 is localized to its nonenzymatic C-terminal α-helical bundle, centered around α-helix 6. The GSTM2-2 binding site is in divergent region 3 (DR3 region) of RyR2. The sequence differences between the DR3 regions of RyR1 and RyR2 explain the specificity of the GSTs for one isoform of the protein. GSTM2-2 is one of the few known endogenous inhibitors of the cardiac RyR and is likely to be important in maintaining low RyR2 activity during diastole. We discuss interactions between a nonenzymatic member of the GST structural family, the CLIC-2 (type 2 chloride intracellular channel) protein, which inhibits both RyR1 and RyR2. The possibility that the GST and CLIC2 proteins bind to different sites on the RyR, and that different structures within the GST and CLIC proteins bind to RyR channels, is discussed. We conclude that the C-terminal part of GSTM2-2 may provide the basis of a therapeutic compound for use in cardiac disorders.

Objective: In this study, the effect of Asparagus falcatus extract on acetaminophen-induced liver injury was investigated in vivo., Method: Six arms of study. ICR mice (n = 20) were treated with acetaminophen at a single dose of 300 mg/kg (in saline, after a 16-hr fast) to induce hepatotoxicity. Drug control group and pre- and posttreated groups were administered 0.9 g/kg of Asparagus falcatus orally. Serum ALT, AST, ALP, liver GSH, antioxidant enzymes, GPx (glutathione peroxidase), GR (glutathione reductase), GST (glutathione-S-transferase), and liver/serum malondialdehyde (MDA) concentrations were estimated. Liver damage was also assessed histopathologically. The effect of the plant extract was compared with N-acetyl cysteine., Results: Acetaminophen produced liver damage, as manifested by a significant rise (P <. 001, one-way ANOVA) in serum ALT, AST, and ALP, and a reduction (P <. 001) in the liver reduced glutathione (GSH) as compared to respective controls. All enzyme activities and liver GSH were significantly improved in Asparagus-treated mice, with pretreatment providing better results than posttreatment (P <. 05). Histopathologically, mice pretreated with Asparagus showed no liver necrosis. A significant improvement was observed in antioxidant enzyme activities of GPx, GR, and GST in the Asparagus pretreated group (P <. 05). Mice posttreated with Asparagus showed a significant reduction in MDA formation (P <. 05)., Conclusion: These results suggest that the feeding regimen with Asparagus extract inhibited the progression of hepatic injury induced by acetaminophen.