title: Effects of Bisphenol A Metabolite 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene on Lung Function and Type 2 Pulmonary Alveolar Epithelial Cell Growth.
abstract: Bisphenol A (BPA) is recognized as a major pollutant worldwide. 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is a major active metabolite of BPA. The epidemiological and animal studies have reported that BPA is harmful to lung function. The role of MBP in lung dysfunction after BPA exposure still remains unclear. This study investigated whether MBP would induce lung alveolar cell damage and evaluated the role of MBP in the BPA exposure-induced lung dysfunction. An in vitro type 2 alveolar epithelial cell (L2) model and an ex vivo isolated reperfused rat lung model were used to determine the effects of BPA or MBP on cell growth and lung function. MBP, but not BPA, dose-dependently increased the mean artery pressure (Pa), pulmonary capillary pressure (Pc), pulmonary capillary filtration coefficient (Kfc), and wet/dry weight ratio in isolated reperfused rat lungs. MBP significantly reduced cell viability and induced caspases-3/7 cleavage and apoptosis and increased AMP-activated protein kinas (AMPK) phosphorylation and endoplasmic reticulum (ER) stress-related molecules expression in L2 cells, which could be reversed by AMPK-siRNA transfection. These findings demonstrated for the first time that MBP exposure induced type 2 alveolar cell apoptosis and lung dysfunction through an AMPK-regulated ER stress signaling pathway.
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.|Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
authors.forename: Shing-Hwa
authors.initials: SH
authors.lastname: Liu
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, Changhua County, Taiwan.
authors.forename: Chin-Chuan
authors.initials: CC
authors.lastname: Su
authors.affiliation: Department of Emergency, Taichung Tzuchi Hospital, Taichung, Taiwan.
authors.forename: Kuan-I
authors.initials: KI
authors.lastname: Lee
authors.affiliation: Department of Physiology and Graduate Institute of Basic Medical Science, College of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Chen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D056809:Alveolar Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001559:Benzhydryl Compounds / Q000737:chemistry / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010636:Phenols / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D000098826:Bisphenol A Compounds
chemical_list: D055372:AMP-Activated Protein Kinases; D001559:Benzhydryl Compounds; D053148:Caspase 3; D053179:Caspase 7; D010636:Phenols; D034741:RNA, Small Interfering; C504750:4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene; C006780:bisphenol A; D000098826:Bisphenol A Compounds