Enhanced protein glutathiolation and oxidative stress in cigarette smokers

Joshua E. Muscat, Wayne Kleinman, Stephen Colosimo, Allison Muir, Philip Lazarus, Jong Park, John P. Richie

Research output: Contribution to journalArticlepeer-review

77 Scopus citations


There are many functional assays of oxidative damage to DNA, protein, and lipids but few reliable markers of chronic oxidative stress. The glutathiolation of proteins at key Cys residues is considered an important redox-sensitive, posttranslational signaling mechanism in the regulation of critical cellular functions. To determine whether protein bound glutathione (GSSP) is a sensitive indicator of oxidative stress, red blood cell and plasma concentrations were measured and compared between smokers and nonsmokers. In a community-based study conducted in Westchester County, New York, USA, blood samples were obtained from 354 cigarette smokers and 97 never smokers. The mean concentration of blood GSSP (μmol/L) was 32% higher in cigarette smokers and 43% higher when standardized by hemoglobin concentrations (p < .01). Plasma GSSP levels were also 20% higher in smokers than in nonsmokers (p < .001). The relationship was dose-dependent, with blood GSSP levels significantly correlated with cigarettes smoked per day, plasma cotinine, and plasma thiocyanate (r values ranged from .25 to .40). In smokers, there were no significant differences in GSSP and GSH levels by GSTM1 or GSTM3 genotype. Intraindividual variation in blood samples, as determined by taking serial samples over a 2-week period, was low (CV = 12.1%, n = 8). GSSP levels are stable over time but increase in response to the abundant free radicals in cigarette smoke. These findings support the use of GSSP as a sensitive biomarker of oxidative stress.

Original languageEnglish (US)
Pages (from-to)464-470
Number of pages7
JournalFree Radical Biology and Medicine
Issue number4
StatePublished - Feb 15 2004

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)


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