PMID- 12485413
OWN - NLM
STAT- MEDLINE
DCOM- 20030123
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 84
IP  - 1
DP  - 2003 Jan
TI  - HIV-Tat protein induces oxidative and inflammatory pathways in brain endothelium.
PG  - 169-79
AB  - Impaired function of the brain vasculature might contribute to the development of 
      HIV-associated dementia. For example, injury or dysfunction of brain 
      microvascular endothelial cells (BMEC) can lead to the breakdown of the 
      blood-brain barrier (BBB) and thus allow accelerated entry of the HIV-1 virus 
      into the CNS. Mechanisms of injury to BMEC during HIV-1 infection are not fully 
      understood, but the viral gene product Tat may be, at least in part, responsible 
      for this effect. Tat can be released from infected perivascular macrophages in 
      the CNS of patients with AIDS, and thus BMEC can be directly exposed to high 
      concentrations of this protein. To study oxidative and inflammatory mechanisms 
      associated with Tat-induced toxicity, BMEC were exposed to increasing doses of 
      Tat1-72, and markers of oxidative stress, as well as redox-responsive 
      transcription factors such as nuclear factor-kappaB (NF-kappaB) and activator 
      protein-1 (AP-1), were measured. Tat1-72 treatment markedly increased cellular 
      oxidative stress, decreased levels of intracellular glutathione and activated DNA 
      binding activity and transactivation of NF-kappaB and AP-1. To determine if 
      Tat1-72 can stimulate inflammatory responses in brain endothelium in vivo, 
      expression of monocyte chemoattractant protein-1 (MCP-1), an NF-kappaB and 
      AP-1-dependent chemokine, was studied in brain tissue in mice injected with 
      Tat1-72 into the right hippocampus. Tat1-72 markedly elevated the MCP-1 mRNA 
      levels in brain tissue. In addition, a double immunohistochemistry study revealed 
      that MCP-1 protein was markedly overexpressed on brain vascular endothelium. 
      These data indicate that Tat1-72 can induce redox-related inflammatory responses 
      both in in vitro and in vivo environments. These changes can directly lead to 
      disruption of the BBB. Thus, Tat can play an important role in the development of 
      detrimental vascular changes in the brains of HIV-infected patients.
FAU - Toborek, Michal
AU  - Toborek M
AD  - Department of Surgery, Animal Sciences and Neurology, University of Kentucky 
      Medical Center, Lexington, Kentucky 40536, USA. mjtobo00@pop.uky.edu
FAU - Lee, Yong Woo
AU  - Lee YW
FAU - Pu, Hong
AU  - Pu H
FAU - Malecki, Andrzej
AU  - Malecki A
FAU - Flora, Govinder
AU  - Flora G
FAU - Garrido, Rosario
AU  - Garrido R
FAU - Hennig, Bernhard
AU  - Hennig B
FAU - Bauer, Hans-Christian
AU  - Bauer HC
FAU - Nath, Avindra
AU  - Nath A
LA  - eng
GR  - P42 ES007380/ES/NIEHS NIH HHS/United States
GR  - AA013843/AA/NIAAA NIH HHS/United States
GR  - MH63022/MH/NIMH NIH HHS/United States
GR  - NS39254/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Chemokine CCL2)
RN  - 0 (Gene Products, tat)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (tat Gene Products, Human Immunodeficiency Virus)
RN  - 0 (tat peptide (1-72), Human immunodeficiency virus 1)
SB  - IM
MH  - Animals
MH  - *Cerebrovascular Circulation/*drug effects
MH  - Chemokine CCL2/genetics
MH  - Clone Cells
MH  - Endothelium, Vascular/*drug effects/metabolism
MH  - Gene Products, tat/*pharmacology
MH  - Microcirculation/drug effects
MH  - NF-kappa B/physiology
MH  - *Oxidative Stress
MH  - RNA, Messenger/metabolism
MH  - Swine
MH  - Transcription Factor AP-1/physiology
MH  - Transcriptional Activation/drug effects
MH  - Vasculitis/*chemically induced/metabolism
MH  - tat Gene Products, Human Immunodeficiency Virus
EDAT- 2002/12/18 04:00
MHDA- 2003/01/24 04:00
CRDT- 2002/12/18 04:00
PHST- 2002/12/18 04:00 [pubmed]
PHST- 2003/01/24 04:00 [medline]
PHST- 2002/12/18 04:00 [entrez]
AID - 1543 [pii]
AID - 10.1046/j.1471-4159.2003.01543.x [doi]
PST - ppublish
SO  - J Neurochem. 2003 Jan;84(1):169-79. doi: 10.1046/j.1471-4159.2003.01543.x.