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L-gamma-Glutamyl-L-cysteinyl-glycine (glutathione; GSH) and GSH-related enzymes in the regulation of pro- and anti-inflammatory cytokines: a signaling transcriptional scenario for redox(y) immunologic sensor(s)?
Mol Immunol. 2005 May; 42(9):987-1014.MI

Abstract

Of the antioxidant/prooxidant mechanisms mediating the regulation of inflammatory mediators, particularly cytokines, oxidative stress-related pathways remain a cornerstone. It is conspicuous that there is a strong association between free radical accumulation (ROS/RNS; oxidative stress) and the evolution of inflammation and inflammatory-related responses. The scenario that upholds a consensus on the aforementioned is still evolving to unravel, from an immunologic perspective, the molecular mechanisms associated with ROS/RNS-dependent inflammation. Cytokines are keynote players when it comes to defining an intimate relationship among reduction-oxidation (redox) signals, oxidative stress and inflammation. How close we are to identifying the molecular basis of this intricate association should be weighed against the involvement of specific signaling molecules and, potentially, transcription factors. L-gamma-Glutamyl-L-cysteinyl-glycine, or glutathione (GSH), an antioxidant thiol, has shaped, and still is refining, the face of oxidative signaling in terms of regulating the milieu of inflammatory mediators, ostensibly via the modulation (expression/repression) of oxygen- and redox-responsive transcription factors, hence termed redox(y)-sensitive cofactors. When it comes to the arena of oxygen sensing, oxidative stress and inflammation, nuclear factor-kappaB (NF-kappaB) and hypoxia-inducible factor-1alpha (HIF-1alpha) are key players that determine antioxidant/prooxidant responses with oxidative challenge. It is the theme therein to underlie current understanding of the molecular association hanging between oxidative stress and the evolution of inflammation, walked through an elaborate discussion on the role of transcription factors and cofactors. Would that classify glutathione and other redox signaling cofactors as potential anti-inflammatory molecules emphatically remains of particular interest, especially in the light of identifying upstream and downstream molecular pathways for conceiving therapeutic, alleviating strategy for oxidant-mediated, inflammatory-related disease conditions.

Authors+Show Affiliations

Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon. johnjhaddad@yahoo.co.ukNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

15829290

Citation

Haddad, John J., and Hisham L. Harb. "L-gamma-Glutamyl-L-cysteinyl-glycine (glutathione; GSH) and GSH-related Enzymes in the Regulation of Pro- and Anti-inflammatory Cytokines: a Signaling Transcriptional Scenario for Redox(y) Immunologic Sensor(s)?" Molecular Immunology, vol. 42, no. 9, 2005, pp. 987-1014.
Haddad JJ, Harb HL. L-gamma-Glutamyl-L-cysteinyl-glycine (glutathione; GSH) and GSH-related enzymes in the regulation of pro- and anti-inflammatory cytokines: a signaling transcriptional scenario for redox(y) immunologic sensor(s)? Mol Immunol. 2005;42(9):987-1014.
Haddad, J. J., & Harb, H. L. (2005). L-gamma-Glutamyl-L-cysteinyl-glycine (glutathione; GSH) and GSH-related enzymes in the regulation of pro- and anti-inflammatory cytokines: a signaling transcriptional scenario for redox(y) immunologic sensor(s)? Molecular Immunology, 42(9), 987-1014.
Haddad JJ, Harb HL. L-gamma-Glutamyl-L-cysteinyl-glycine (glutathione; GSH) and GSH-related Enzymes in the Regulation of Pro- and Anti-inflammatory Cytokines: a Signaling Transcriptional Scenario for Redox(y) Immunologic Sensor(s). Mol Immunol. 2005;42(9):987-1014. PubMed PMID: 15829290.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - L-gamma-Glutamyl-L-cysteinyl-glycine (glutathione; GSH) and GSH-related enzymes in the regulation of pro- and anti-inflammatory cytokines: a signaling transcriptional scenario for redox(y) immunologic sensor(s)? AU - Haddad,John J, AU - Harb,Hisham L, Y1 - 2004/11/23/ PY - 2004/09/01/received PY - 2004/09/29/accepted PY - 2005/4/15/pubmed PY - 2005/7/13/medline PY - 2005/4/15/entrez SP - 987 EP - 1014 JF - Molecular immunology JO - Mol Immunol VL - 42 IS - 9 N2 - Of the antioxidant/prooxidant mechanisms mediating the regulation of inflammatory mediators, particularly cytokines, oxidative stress-related pathways remain a cornerstone. It is conspicuous that there is a strong association between free radical accumulation (ROS/RNS; oxidative stress) and the evolution of inflammation and inflammatory-related responses. The scenario that upholds a consensus on the aforementioned is still evolving to unravel, from an immunologic perspective, the molecular mechanisms associated with ROS/RNS-dependent inflammation. Cytokines are keynote players when it comes to defining an intimate relationship among reduction-oxidation (redox) signals, oxidative stress and inflammation. How close we are to identifying the molecular basis of this intricate association should be weighed against the involvement of specific signaling molecules and, potentially, transcription factors. L-gamma-Glutamyl-L-cysteinyl-glycine, or glutathione (GSH), an antioxidant thiol, has shaped, and still is refining, the face of oxidative signaling in terms of regulating the milieu of inflammatory mediators, ostensibly via the modulation (expression/repression) of oxygen- and redox-responsive transcription factors, hence termed redox(y)-sensitive cofactors. When it comes to the arena of oxygen sensing, oxidative stress and inflammation, nuclear factor-kappaB (NF-kappaB) and hypoxia-inducible factor-1alpha (HIF-1alpha) are key players that determine antioxidant/prooxidant responses with oxidative challenge. It is the theme therein to underlie current understanding of the molecular association hanging between oxidative stress and the evolution of inflammation, walked through an elaborate discussion on the role of transcription factors and cofactors. Would that classify glutathione and other redox signaling cofactors as potential anti-inflammatory molecules emphatically remains of particular interest, especially in the light of identifying upstream and downstream molecular pathways for conceiving therapeutic, alleviating strategy for oxidant-mediated, inflammatory-related disease conditions. SN - 0161-5890 UR - https://www.unboundmedicine.com/medline/citation/15829290/L_gamma_Glutamyl_L_cysteinyl_glycine__glutathione L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-5890(04)00423-7 DB - PRIME DP - Unbound Medicine ER -