title: Cigarette smoke extract induces endothelial cell injury via JNK pathway.
abstract: Cigarette smoking is the most crucial factor responsible for chronic obstructive pulmonary disease (COPD). The precise mechanisms of the development of the disease have, however, not been fully understood. Recently, impairment of pulmonary endothelial cells has been increasingly recognized as a critical pathophysiological process in COPD. To verify this hypothesis, we examined how cigarette smoke extract (CSE) damages human umbilical vein endothelial cells (HUVECs). CSE activated c-Jun N-terminal kinase (JNK), and treatment of HUVECs with SP600125, a specific inhibitor of the JNK pathway, significantly suppressed endothelial cell damage by CSE. In contrast, inhibition of the extracellular-regulated kinase or the p38 pathway did not affect the cytotoxicity of CSE. Furthermore, anti-oxidants superoxide dismutase and catalase reduced CSE-induced JNK phosphorylation and endothelial cell injury. These results indicate that CSE damages vascular endothelial cells through the JNK pathway activated, at least partially, by oxidative stress.
authors.affiliation: Department of Molecular Medicine, Osaka University Graduate School of Medicine, 2-2, Yamada-oka, Suita, Osaka, Japan.
authors.forename: Shigenori
authors.initials: S
authors.lastname: Hoshino
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoshida
authors.forename: Koji
authors.initials: K
authors.lastname: Inoue
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Yano
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yanagita
authors.forename: Hidenori
authors.initials: H
authors.lastname: Mawatari
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamane
authors.forename: Takashi
authors.initials: T
authors.lastname: Kijima
authors.forename: Toru
authors.initials: T
authors.lastname: Kumagai
authors.forename: Tadashi
authors.initials: T
authors.lastname: Osaki
authors.forename: Isao
authors.initials: I
authors.lastname: Tachiba
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kawase
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D004249:DNA Damage; D042783:Endothelial Cells / Q000201:enzymology / Q000473:pathology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology*; D018384:Oxidative Stress; D010766:Phosphorylation; D012907:Smoking; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology / Q000201:enzymology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000873:Anthracenes; D000975:Antioxidants; D004791:Enzyme Inhibitors; C432165:pyrazolanthrone; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases