Particulate phase cigarette smoke increases MnSOD, NQO1, and CINC-1 in rat lungs.
Loss of antioxidant/oxidant homeostasis perpetuates inflammation in the lungs and may contribute to the development of COPD and lung cancer. Cigarette smoke (CS) is a primary source of airway oxidative stress and recruits inflammatory cells into smokers' lungs. However, whether these consequences are attributable to a specific or the collective fraction of CS is unknown. We investigated whether the particulate or the gas phase of CS would alter expression of the antioxidant enzymes MnSOD and NQO1 or CINC-1. Sprague Dawley rats were exposed to sham (n = 10) or the particulate phase (PP; n = 10) or gas phase (n = 10) of a Kentucky reference cigarette (1R4F) for 2 h/d for 28 d, after which animals were sacrificed and the lower left lobe of the lung was removed. Immunoblots for SOD and NQO1 revealed that lungs exposed to PP had higher MnSOD/actin and NQO1/actin ratios than either sham-or gas phase-treated animals. In contrast, CuZnSOD remained unchanged. In PP-exposed animals, CINC-1 was 3-fold higher than in sham-exposed animals. The increases in MnSOD and NQO1 protein were associated with increases in total SOD, NQO1, and MPO activities. These data provide evidence that the PP of CS alters oxidant/antioxidant homeostasis in the lungs and participates in the pathogenesis of CS-induced lung diseases such as COPD and cancer.
Stringer
Kathleen A
KA
Department of Clinical Pharmacy, School of Pharmacy, C238, 4200 East Ninth Avenue, Denver, CO 80262, USA. kathleen.stringer@uchsc.edu
Freed
Brian M
BM
Dunn
John S
JS
Sayers
Scott
S
Gustafson
Daniel L
DL
Flores
Sonia C
SC
D000818:Animals; D015153:Blotting, Western; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000378:metabolism*; D004789:Enzyme Activation; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008168:Lung / Q000201:enzymology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking / Q000009:adverse effects*; D013482:Superoxide Dismutase / Q000378:metabolism*
D054360:Chemokine CXCL1; D019743:Chemokines, CXC; C513297:Cxcl1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D013482:Superoxide Dismutase; D016660:NAD(P)H Dehydrogenase (Quinone)