Cigarette smoke extract induces endothelial cell injury via JNK pathway.
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.
Hoshino
Shigenori
S
Department of Molecular Medicine, Osaka University Graduate School of Medicine, 2-2, Yamada-oka, Suita, Osaka, Japan.
Yoshida
Mitsuhiro
M
Inoue
Koji
K
Yano
Yukihiro
Y
Yanagita
Masahiko
M
Mawatari
Hidenori
H
Yamane
Hiroyuki
H
Kijima
Takashi
T
Kumagai
Toru
T
Osaki
Tadashi
T
Tachiba
Isao
I
Kawase
Ichiro
I
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
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