Document Detail


Methamphetamine induces AP-1 and NF-kappaB binding and transactivation in human brain endothelial cells.
MedLine Citation:
PMID:  11746378     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cellular and molecular mechanisms of methamphetamine (METH)-induced neurotoxicity may involve alterations of cellular redox status and induction of inflammatory genes in endothelial cells. To study these hypotheses, molecular signaling pathways of METH-induced inflammatory responses via activation of redox-sensitive transcription factors were investigated in human brain microvascular endothelial cells (HBMEC). A dose-dependent depletion of total glutathione levels was detected in HBMEC exposed to METH. In addition, electrophoretic mobility shift assay (EMSA) showed significant increases in DNA binding activities of redox-responsive transcription factors, AP-1 and NF-kappaB, in HBMEC treated with METH. METH-mediated AP-1 or NF-kappaB activation was accompanied by induction of transactivation of AP-1 or NF-kappaB, as measured by dual luciferase assay using specific reporter plasmids. Because NF-kappaB and AP-1 are known to regulate expression of inflammatory genes, expression of the gene encoding for tumor necrosis factor-alpha (TNF-alpha) was also studied in METH-treated HBMEC. A dose-dependent overexpression of the TNF-alpha gene was observed in HBMEC treated with METH. The importance of AP-1 and NF-kappaB in METH-induced TNF-alpha gene was confirmed in functional promoter studies using constructs of the TNF-alpha promoter with mutated AP-1 or NF-kappaB sites. These results indicate that METH-induced disturbances in cellular redox status and activation of AP-1 and NF-kappaB can play critical roles in the signaling pathways leading to upregulation of inflammatory genes in human brain endothelial cells.
Authors:
Y W Lee; B Hennig; J Yao; M Toborek
Related Documents :
16905118 - Splice variants of miap1 have an enhanced ability to inhibit apoptosis.
15878398 - Increase of intracellular glutathione by low-level no mediated by transcription factor ...
20182598 - The regulatory logic of the nf-kappab signaling system.
11310828 - Nuclear factor-kappab regulates cyclooxygenase-2 expression and cell proliferation in h...
22302208 - Combination therapy with an angiotensin ii receptor blocker and an hmg-coa reductase in...
11906908 - Onset of steroidogenic enzyme gene expression during ovarian follicular development in ...
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  66     ISSN:  0360-4012     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-12-17     Completed Date:  2002-01-24     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  583-91     Citation Subset:  IM    
Copyright Information:
Copyright 2001 Wiley-Liss, Inc.
Affiliation:
Department of Surgery, University of Kentucky Medical Center, Lexington, Kentucky 40536, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Amphetamine-Related Disorders / genetics,  metabolism,  physiopathology
Binding Sites / drug effects,  physiology
Blood-Brain Barrier / drug effects,  physiology
Brain / drug effects*,  metabolism,  physiopathology
Cells, Cultured / drug effects,  metabolism
Encephalitis / chemically induced,  genetics*,  metabolism
Endothelium, Vascular / drug effects*,  metabolism,  physiopathology
Gene Expression Regulation / drug effects,  physiology
Genes, Reporter / drug effects,  physiology
Glutathione / drug effects,  metabolism
Humans
Methamphetamine / toxicity*
Microcirculation / drug effects,  metabolism,  physiopathology
NF-kappa B / drug effects*,  genetics,  metabolism
Oxidation-Reduction / drug effects
Oxidative Stress / drug effects*,  genetics
RNA, Messenger / drug effects,  metabolism
Signal Transduction / drug effects,  genetics
Transcription Factor AP-1 / drug effects*,  genetics,  metabolism
Transcription, Genetic / drug effects,  physiology
Transfection
Tumor Necrosis Factor-alpha / drug effects,  genetics,  metabolism
Grant Support
ID/Acronym/Agency:
NS39254-01A1/NS/NINDS NIH HHS; NS39254-01A1S1/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/NF-kappa B; 0/RNA, Messenger; 0/Transcription Factor AP-1; 0/Tumor Necrosis Factor-alpha; 537-46-2/Methamphetamine; 70-18-8/Glutathione

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


Previous Document:  Early formation of mature amyloid-beta protein deposits in a mutant APP transgenic model depends on ...
Next Document:  PKC and PKA, but not PKG mediate LPS-induced CGRP release and [Ca(2+)](i) elevation in DRG neurons o...