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HIV‐1 Tat protein disrupts the blood–brain barrier through the oxidative and inflammatory mechanisms
Author(s) -
Toborek M.,
Pu H.,
Andras I.,
Flora G.,
Lee Y. W.
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.85.s2.16_7.x
Subject(s) - blood–brain barrier , microbiology and biotechnology , inflammation , oxidative stress , tight junction , monocyte , biology , transcription factor , in vitro , infiltration (hvac) , in vivo , immunology , central nervous system , chemistry , neuroscience , biochemistry , gene , physics , thermodynamics
Tat protein, which is released from HIV‐infected cells, may play a major role in HIV‐induced pathological processes in the CNS, including HIV‐associated dementia. Therefore, the aim of the present study was to examine the effects of Tat on vascular inflammatory responses as well as blood–brain barrier structure and function both in vitro and in vivo environments. Tat treatment induced cellular oxidative processes, activities of redox‐regulated transcription factors, and expression of inflammatory mediators. Most importantly, Tat disrupted the blood–brain barrier and stimulated monocyte infiltration of the CNS. Disruption tight junction protein integrity appeared to be the underlying mechanism of these effects. Among studied junctional proteins, claudin 5 expression was the most affected by Tat treatment. These data provide evidence that Tat can be involved in the blood–brain barrier breakdown and HIV entry into the brain. Acknowledgements: Supported by NIH; NS39254, MH63022, and AA013843.