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Extracellular communication and signaling by thiol/disulfide redox states
Author(s) -
Jones Dean P.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.196.1
Subject(s) - extracellular , disulfide bond , redox , thiol , chemistry , microbiology and biotechnology , biochemistry , biology , inorganic chemistry
Extracellular cysteine/cystine (Cys/CySS) and GSH/GSSG couples provide redox communication between organ systems. Both are highly regulated in healthy individuals. Cys and CySS are more abundant in human plasma, regulated by cell efflux and uptake mechanisms. Oxidized redox potentials (EhCySS and EhGSSG) and high CySS are associated with risk factors for cardiovascular disease (CVD), including aging, smoking, type 2 diabetes, obesity, and alcohol abuse. Oxidized EhCySS activates proinflammatory signaling through cell surface protein thiols, signals mitochondrial oxidant production, activates NF‐κB and Nrf‐2, and elevates proinflammatory cytokines, proapoptotic proteins, cell adhesion molecules and detoxification proteins. Reduced EhCySS stimulates cell proliferation and cell survival signaling in multiple cell types. The critical nature of these signaling mechanisms supports the use of plasma levels of Cys, CySS, and EhCySS as key indicators of systemic oxidative stress. Pharmacologic interventions to control or improve EhCySS may prove useful to prevent CVD and other age‐associated disease processes.