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.
Hageman
Geja J
GJ
Department of Health Risk Analysis and Toxicology, Research Institute NUTRIM, University of Maastricht, Maastricht, Netherlands. g.hageman@grat.unimaas.nl
Larik
Ingrid
I
Pennings
Herman Jan
HJ
Haenen
Guido R M M
GR
Wouters
Emiel F M
EF
Bast
Aalt
A
D000975:Antioxidants / Q000032:analysis; D002908:Chronic Disease; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009243:NAD / Q000097:blood / Q000378:metabolism; D018384:Oxidative Stress; D011065:Poly(ADP-ribose) Polymerases / Q000097:blood / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*
D000975:Antioxidants; D009243:NAD; D011065:Poly(ADP-ribose) Polymerases