Short-term cigarette smoke exposure induces reversible changes in energy metabolism and cellular redox status independent of inflammatory responses in mouse lungs.
Cigarette smoking leads to alteration in cellular redox status, a hallmark in the pathogenesis of chronic obstructive pulmonary disease. This study examines the role of cigarette smoke (CS) exposure in the impairment of energy metabolism and, consequently, mitochondrial dysfunction. Male A/J mice were exposed to CS generated by a smoking machine for 4 or 8 wk. A recovery group was exposed to CS for 8 wk and allowed to recover for 2 wk. Acute CS exposure altered lung glucose metabolism, entailing a decrease in the rate of glycolysis and an increase in the pentose phosphate pathway, as evidenced by altered expression and activity of GAPDH and glucose-6-phosphate dehydrogenase, respectively. Impairment of GAPDH was found to be due to glutathionylation of its catalytic site cysteines. Metabolic changes were associated with changes in cellular and mitochondrial redox status, assessed in terms of pyridine nucleotides and glutathione. CS exposure elicited an upregulation of the expression of complexes II, III, IV, and V and of the activity of complexes II, IV, and V. Microarray analysis of gene expression in mouse lungs after exposure to CS for 8 wk revealed upregulation of a group of genes involved in metabolism, electron transfer chain, oxidative phosphorylation, mitochondrial transport and dynamics, and redox regulation. These changes occurred independently of inflammatory responses. These findings have implications for the early onset of alterations in energy and redox metabolism upon acute lung exposure to CS.
Pharmacology & Pharmaceutical Sciences, School of Pharmacy, Univ. of Southern California, Los Angeles, CA 90089-9121, USA.
Amit R
AR
Agarwal
Liqin
L
Zhao
Harsh
H
Sancheti
Isaac K
IK
Sundar
Irfan
I
Rahman
Enrique
E
Cadenas
D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D024602:Glyceraldehyde-3-Phosphate Dehydrogenase (NADP+)(Phosphorylating) / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D017494:Proton Pumps / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D017494:Proton Pumps; D014028:Tobacco Smoke Pollution; D005954:Glucosephosphate Dehydrogenase; D024602:Glyceraldehyde-3-Phosphate Dehydrogenase (NADP+)(Phosphorylating); D005947:Glucose