Short-term cigarette smoke exposure induces reversible changes in energy metabolism and cellular redox status independent of inflammatory responses in mouse lungs

Amit R Agarwal, Liqin Zhao, Harsh Sancheti, Isaac K Sundar, Irfan Rahman, Enrique Cadenas

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)L889-98
Number of pages10
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume303
Issue number10
DOIs
Publication statusPublished - Nov 2012

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