Document Detail


Cigarette smoke extract induces HO-1 expression in mouse cerebral vascular endothelial cells: involvement of c-Src/NADPH oxidase/PDGFR/JAK2/STAT3 pathway.
MedLine Citation:
PMID:  20568122     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Several chemicals present in cigarette smoke (CS) have been reported to induce heme oxygenase-1 (HO-1) expression, which represents a prime defense mechanism in protecting the cells from stress-dependent adverse effects on peripheral vascular system. However, the effects of cigarette smoke extract (CSE) on HO-1 induction and the mechanisms underlying CSE-induced HO-1 expression in brain vessels are not completely understood. Here, we used a mouse brain endothelial cell culture (bEnd.3) to investigate the effect of CSE on HO-1 induction and the mechanisms underlying CSE-induced HO-1 expression in cerebral vessels. We demonstrated that sublethal concentrations of CSE (30 µg/ml) induced submaximal HO-1 expression in bEnd.3 cells. NADPH oxidase-dependent ROS generation played a key role in CSE-induced HO-1 expression. CSE-induced HO-1 expression was mediated through PDGFR/JAK2/STAT3 cascade, which was observed by pretreatment with the respective pharmacological inhibitors or transfection with PDGFR shRNA. CSE activated NADPH oxidase through c-Src in bEnd.3 cells. Taken together, these results suggested that, in bEnd.3 cells, CSE-induced HO-1 expression was mediated through PDGFR/JAK2/STAT3 cascade, which was regulated by c-Src or c-Src activated-NADPH oxidase/ROS.
Authors:
Ruey-Horng Shih; I-Ta Lee; Hsi-Lung Hsieh; Yu Ru Kou; Chuen-Mao Yang
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  225     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-09-15     Completed Date:  2010-10-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  741-50     Citation Subset:  IM    
Copyright Information:
© 2010 Wiley-Liss, Inc.
Affiliation:
Department of Physiology and Pharmacology, Chang Gung University, Tao-Yuan, Taiwan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Binding Sites
Brain / blood supply*
Cells, Cultured
Endothelial Cells / drug effects*,  enzymology
Enzyme Induction
Enzyme Inhibitors / pharmacology
Free Radical Scavengers / pharmacology
Heme Oxygenase-1 / biosynthesis*,  genetics
Janus Kinase 2 / metabolism*
Membrane Proteins / biosynthesis*,  genetics
Mice
NADPH Oxidase / metabolism*
Promoter Regions, Genetic
RNA Interference
RNA, Messenger / biosynthesis
Reactive Oxygen Species / metabolism
Receptors, Platelet-Derived Growth Factor / genetics,  metabolism*
STAT3 Transcription Factor / metabolism*
Signal Transduction / drug effects
Smoke*
Smoking / adverse effects*
Time Factors
src-Family Kinases / metabolism*
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Free Radical Scavengers; 0/Membrane Proteins; 0/RNA, Messenger; 0/Reactive Oxygen Species; 0/STAT3 Transcription Factor; 0/Smoke; 0/Stat3 protein, mouse; EC 1.14.99.3/Heme Oxygenase-1; EC 1.14.99.3/Hmox1 protein, mouse; EC 1.6.3.1/NADPH Oxidase; EC 2.7.1.112/Jak2 protein, mouse; EC 2.7.10.1/Janus Kinase 2; EC 2.7.10.1/Receptors, Platelet-Derived Growth Factor; EC 2.7.10.2/src-Family Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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