Systemic poly(ADP-ribose) polymerase-1 activation, chronic inflammation, and oxidative stress in COPD patients

Oxidative stress and systemic inflammation in chronic obstructive pulmonary disease (COPD) strongly suggest a role for the nuclear enzyme poly(ADP-ribose) polymerase-1 (PARP-1, E.C.2.4.2.30) in the disease pathophysiology. PARP-1 is highly activated by reactive oxygen species-induced DNA strand breaks, upon which it forms extensive poly(ADP-ribose) (PAR) polymers from its substrate NAD+. We hypothesized that in COPD, chronic inflammation and oxidative stress would lead to systemic PARP-1 activation and to a reduced NAD+ status. In a patient-control study, systemic PARP-1 activation was assessed by immunofluorescent detection of PAR polymers in peripheral blood lymphocytes. The percentage of PAR polymer-positive lymphocytes appeared to be higher in COPD patients (27 ± 3%) than in healthy age-matched controls (17 ± 2%, p < .05). Trolox equivalent antioxidant capacity (TEAC) of deproteinized plasma (p < .001), plasma uric acid (p < .05), as well as blood NAD+ (p < .01) of stable COPD patients were significantly reduced when compared to controls. In addition, levels of proinflammatory cytokines IL-6, IL-8, and sICAM-1 were increased (p < .005) in COPD patients. In this study, evidence was found for the presence of systemic inflammation, chronic oxidative stress, and systemic PARP-1 activation in stable COPD patients. These data support a contribution of oxidative stress-induced PARP-1 activation to the pathophysiology of COPD.