Cocaine activates redox-regulated transcription factors and induces TNF-α expression in human brain endothelial cells

Yong Woo Lee, Bernhard Hennig, Milan Fiala, Kwang Sik Kim, Michal J Toborek

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Cocaine abuse is frequently associated with cerebrovascular pathology. Although the cellular and molecular mechanisms of these alterations are not fully understood, they may involve oxidative injury or dysfunction of brain microvascular endothelial cells. To test this hypothesis, total glutathione levels, activation of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), as well as induction of the TNF-α gene expression were determined in human brain microvascular endothelial cells (HBMEC) exposed to cocaine. Exposure of HBMEC to cocaine resulted in a dose-dependent depletion of total glutathione levels. In addition, cocaine markedly activated redox-regulated transcription factors, NF-κB and AP-1. Activation of these transcription factors was accompanied by induction of AP-1- or NF-κB-dependent transcription, as measured by dual luciferase assay in HBMEC transfected with the AP-1- or NF-κB-responsive reporter constructs. Furthermore, HBMEC treatment with cocaine induced a dose-dependent expression of the tumor necrosis factor-α (TNF-α) gene. These results indicate that exposure to cocaine can trigger inflammatory pathways via activation of redox-sensitive transcription factors and induction of expression of the inflammatory genes in HBMEC. These events may contribute to the cerebrovascular insults observed in cocaine-abused patients.

Original languageEnglish
Pages (from-to)125-133
Number of pages9
JournalBrain Research
Volume920
Issue number1-2
DOIs
StatePublished - Nov 30 2001
Externally publishedYes

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Cocaine
Oxidation-Reduction
Transcription Factors
Endothelial Cells
Tumor Necrosis Factor-alpha
Transcription Factor AP-1
Brain
Glutathione
Gene Expression
Cocaine-Related Disorders
Luciferases
Pathology
Wounds and Injuries
Genes

Keywords

  • Abused drug
  • Blood-brain barrier
  • Inflamatory response

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Cocaine activates redox-regulated transcription factors and induces TNF-α expression in human brain endothelial cells. / Lee, Yong Woo; Hennig, Bernhard; Fiala, Milan; Kim, Kwang Sik; Toborek, Michal J.

In: Brain Research, Vol. 920, No. 1-2, 30.11.2001, p. 125-133.

Research output: Contribution to journalArticle

Lee, Yong Woo ; Hennig, Bernhard ; Fiala, Milan ; Kim, Kwang Sik ; Toborek, Michal J. / Cocaine activates redox-regulated transcription factors and induces TNF-α expression in human brain endothelial cells. In: Brain Research. 2001 ; Vol. 920, No. 1-2. pp. 125-133.
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