Nitration of Tyrosine 92 Mediates the Activation of Rat Microsomal Glutathione S-Transferase by Peroxynitrite

Ji, Yin; Neverova, Irina; Eyk, Jennifer E. Van; Bennett, Brian M.

doi:10.1074/jbc.m509480200

Cited by 62 publications

(38 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…MGST1 as a constitutively expressed enzyme, catalyzes the reaction of glutathione with a range of xenobiotic and endogenous electrophiles, reduces the products from lipid peroxidation, and serves mainly as an important detoxication enzyme in the liver [14,30,31]. The expression of MGST1 is relatively stable.…”

Section: Discussionmentioning

confidence: 98%

“…In contrast to the cytosolic GSTs, an important characteristic of MGST1 lies in the posttranslational modi cations on the enzyme regulating its catalytic activities. Under physiological conditions, MGST1 displays very limited activities; however, a variety of posttranslational modi cations including alkylation, nitration, dimerization, etc., could signi cantly enhance its activities and cause enzyme activation [14,15]. Peroxynitrite (ONOO -) is one of the RNS and can regulate many protein functions via posttranslational modi cations [32].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

MAPEG Expression in Mouse Embryonic Stem Cell-Derived Hepatic Tissue System

Zhu

Huang

et al. 2008

Stem Cells and Development

View full text Add to dashboard Cite

The expressions of membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG), a superfamily involved in both inflammation and cell protection, were investigated in an in vitro system of mouse embryonic stem (ES) cell-derived hepatic tissue. Gene expressions of all MAPEG members were demonstrated in a developmental-dependent manner in the derived hepatic tissue. The protein expression of microsomal glutathione S-transferase 1 (MGST1) was not detected until differentiating day 14. It gradually increased by maturation of hepatic tissue. The microsomes of ES cell-derived hepatic tissue possessed the MGST1-like catalytic activity. However, MGST1 from the microsome preparation could not form dimers as usual when exposed to reactive nitrogen species ONOO. Among the other members in MAPEG, weak expressions of leukotriene C(4) synthase (LTC(4)S) and microsomal prostaglandin E synthase 1 (mPGES-1) were observed. A stable expression of 5-Lipoxygenase activating protein (FLAP) appeared during the entire course of differentiation. MGST2 and MGST3 failed to express in the derived hepatic tissue, although mRNA of them do existed. In conclusion, ES cell-derived hepatic tissue possess MAPEG gene expression features, but not all protein expression could be detected, which helps to understand not only the nature of the tissue derived, but also the fate of bioartificial liver system, and may as well provide a valuable in vitro model for research in both inflammation process and toxic events in hepatological fields.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

MAPEG Expression in Mouse Embryonic Stem Cell-Derived Hepatic Tissue System

Zhu

Huang

et al. 2008

Stem Cells and Development

View full text Add to dashboard Cite

show abstract

“…However, nitration at Tyr92 was shown to be critical in functional change as another example of gain in protein function. This conclusion was evidenced by site directed mutagenesis of each Tyr residue of GST-1, overexpression of each GST-1 mutant in LLC-PK1 cells, and then exposure to peroxynitrite followed by monitoring its activity [41]. The activation of GST-1 nitrated at Tyr92 would improve the antioxidant defense.…”

Section: Functional Consequences Of Protein Nitration In Acute Andmentioning

confidence: 99%

Functional Roles of Protein Nitration in Acute and Chronic Liver Diseases

Abdelmegeed

Song

2014

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Nitric oxide, when combined with superoxide, produces peroxynitrite, which is known to be an important mediator for a number of diseases including various liver diseases. Peroxynitrite can modify tyrosine residue(s) of many proteins resulting in protein nitration, which may alter structure and function of each target protein. Various proteomics and immunological methods including mass spectrometry combined with both high pressure liquid chromatography and 2D PAGE have been employed to identify and characterize nitrated proteins from pathological tissue samples to determine their roles. However, these methods contain a few technical problems such as low efficiencies with the detection of a limited number of nitrated proteins and labor intensiveness. Therefore, a systematic approach to efficiently identify nitrated proteins and characterize their functional roles is likely to shed new insights into understanding of the mechanisms of hepatic disease pathophysiology and subsequent development of new therapeutics. The aims of this review are to briefly describe the mechanisms of hepatic diseases. In addition, we specifically describe a systematic approach to efficiently identify nitrated proteins to study their causal roles or functional consequences in promoting acute and chronic liver diseases including alcoholic and nonalcoholic fatty liver diseases. We finally discuss translational research applications by analyzing nitrated proteins in evaluating the efficacies of potentially beneficial agents to prevent or treat various diseases in the liver and other tissues.

show abstract

“…A characteristic of rat liver MGST1 is that covalent modification (e.g., alkylation by N-ethylmaleimide) of its single cysteine residue (Cys-49) results in a marked increase in enzyme activity. Oxidative modification of Cys-49 also results in increased enzyme activity, and recent data from our laboratory have demonstrated that in addition to oxidative stress, nitrosative stress increases MGST1 activity by tyrosine nitration of Tyr-92 and, to a lesser extent, by nitrosation of Cys-49 (Ji et al, 2002(Ji et al, , 2006Ji and Bennett, 2003). In the present study, our goal was to compare GTN biotransformation by the microsomal and cytosolic GSTs to assess the effect of various modifications of MGST1 on GTN biotransformation and to assess whether MGST1 activity or expression is altered in GTN-tolerant animals.…”

mentioning

confidence: 99%

Biotransformation of Glyceryl Trinitrate by Rat Hepatic Microsomal GlutathioneS-Transferase 1

Bennett²

2006

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

Although the biotransformation of organic nitrates by the cytosolic glutathione S-transferases (GSTs) is well known, the relative contribution of the microsomal GST (MGST1) to nitrate biotransformation has not been described. We therefore compared the denitration of glyceryl trinitrate (GTN) by purified rat liver MGST1 and cytosolic GSTs. Both MGST1 and cytosolic GSTs catalyzed the denitration of GTN, but the activity of MGST1 toward GTN was 2-to 3-fold higher. To mimic oxidative/nitrosative stress in vitro, we treated enzyme preparations with hydrogen peroxide, S-nitrosoglutathione, and peroxynitrite. Both oxidants and nitrating reagents increased the activity of MGST1 toward the GST substrate, 1-chloro-2,4-dinitrobenzene (CDNB) whereas these treatments inhibited GTN denitration by MGST1. Alkylation of the sole cysteine residue of MGST1 by N-ethylmaleimide markedly increased enzyme activity with CDNB as substrate but decreased the rate of GTN denitration. In aortic microsomes from GTN-tolerant animals, there was a decreased abundance of MGST1 dimers and trimers. In hepatic microsomes from GTN-tolerant animals, GTN biotransformation was unaltered whereas the rate of CDNB conjugation was doubled, suggesting that chronic GTN exposure causes structural modifications to the enzyme, resulting in increased activity to certain substrates. Collectively, these data indicate that MGST1 contributes significantly to the biotransformation of GTN and that chemical modification of the microsomal enzyme has differential effects on the catalytic activity toward different substrates.Organic nitrates such as glyceryl trinitrate (GTN) have been used clinically for more than a century in the treatment of angina pectoris and congestive heart failure. It is generally accepted that GTN is a prodrug that requires bioactivation to form nitric oxide (NO), or a closely related species, before activation of guanylyl cyclase, increased cyclic GMP, and vascular smooth muscle relaxation. In addition to this mechanism-based biotransformation of GTN to activators of guanylyl cyclase, the denitration of GTN in vascular and nonvascular tissues to inorganic nitrite anion (NO 2 Ϫ ) and its two dinitrate metabolites, glyceryl-1,2-dinitrate (1,2-GDN) and glyceryl-1,3-dinitrate (1,3-GDN) also occurs. This is catalyzed by a number of proteins and enzymes, including hemoglobin and myoglobin (Bennett et al

show abstract

Nitration of Tyrosine 92 Mediates the Activation of Rat Microsomal Glutathione S-Transferase by Peroxynitrite

Cited by 62 publications

References 28 publications

MAPEG Expression in Mouse Embryonic Stem Cell-Derived Hepatic Tissue System

MAPEG Expression in Mouse Embryonic Stem Cell-Derived Hepatic Tissue System

Functional Roles of Protein Nitration in Acute and Chronic Liver Diseases

Biotransformation of Glyceryl Trinitrate by Rat Hepatic Microsomal GlutathioneS-Transferase 1

Contact Info

Product

Resources

About