TY - JOUR
T1 - Enhanced protein glutathiolation and oxidative stress in cigarette smokers
AU - Muscat, Joshua E.
AU - Kleinman, Wayne
AU - Colosimo, Stephen
AU - Muir, Allison
AU - Lazarus, Philip
AU - Park, Jong
AU - Richie, John P.
N1 - Funding Information:
This work was supported by NIH Grants CA68384 and CA17613.
PY - 2004/2/15
Y1 - 2004/2/15
N2 - 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.
AB - 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.
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U2 - 10.1016/j.freeradbiomed.2003.11.018
DO - 10.1016/j.freeradbiomed.2003.11.018
M3 - Article
C2 - 14975449
AN - SCOPUS:1242328680
SN - 0891-5849
VL - 36
SP - 464
EP - 470
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 4
ER -