title: Short-term cigarette smoke exposure leads to metabolic alterations in lung alveolar cells.
abstract: Cigarette smoke (CS)-induced alveolar destruction and energy metabolism changes are known contributors to the pathophysiology of chronic obstructive pulmonary disease (COPD). This study examines the effect of CS exposure on metabolism in alveolar type II cells. Male A/J mice (8 wk old) were exposed to CS generated from a smoking machine for 4 or 8 weeks, and a recovery group was exposed to CS for 8 weeks and allowed to recover for 2 weeks. Alveolar type II cells were isolated from air- or CS- exposed mice. Acute CS exposure led to a reversible airspace enlargement in A/J mice as measured by the increase in mean linear intercept, indicative of alveolar destruction. The effect of CS exposure on cellular respiration was studied using the XF Extracellular Flux Analyzer. A decrease in respiration while metabolizing glucose was observed in the CS-exposed group, indicating altered glycolysis that was compensated by an increase in palmitate utilization; palmitate utilization was accompanied by an increase in the expression of CD36 and carnitine-palmitoyl transferase 1 in type II alveolar cells for the transport of palmitate into the cells and into mitochondria, respectively. The increase in palmitate use for energy production likely affects the surfactant biosynthesis pathway, as evidenced by the decrease in phosphatidylcholine levels and the increase in phospholipase A2 activity after CS exposure. These findings help our understanding of the mechanism underlying the surfactant deficiency observed in smokers and provide a target to delay the onset of COPD.
authors.affiliation: Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California.
authors.forename: Amit R
authors.initials: AR
authors.lastname: Agarwal
authors.forename: Fei
authors.initials: F
authors.lastname: Yin
authors.forename: Enrique
authors.initials: E
authors.lastname: Cadenas
mesh_terms: D056809:Alveolar Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D019069:Cell Respiration / Q000187:drug effects; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000187:drug effects*; D006019:Glycolysis / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D019570:Inhalation Exposure / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D019308:Palmitic Acid / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D054467:Phospholipases A2 / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D037661:Pulmonary Surfactant-Associated Proteins / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D018955:CD36 Antigens; D010713:Phosphatidylcholines; D037661:Pulmonary Surfactant-Associated Proteins; D012906:Smoke; D019308:Palmitic Acid; D002334:Carnitine O-Palmitoyltransferase; D054467:Phospholipases A2
keywords: alveolar cells; cigarette smoke; mitochondria; palmitate; pulmonary surfactant