The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kim, T.-A.
Right arrow Articles by Avraham, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kim, T.-A.
Right arrow Articles by Avraham, S.
The Journal of Immunology, 2003, 170: 2629-2637.
Copyright © 2003 by The American Association of Immunologists

HIV-1 Tat-Mediated Apoptosis in Human Brain Microvascular Endothelial Cells1

Tae-Aug Kim, Hava Karsenty Avraham, Young-Ho Koh, Shuxian Jiang, In-Woo Park and Shalom Avraham2

Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215

The integrity of the blood-brain barrier (BBB) is critical for normal brain function. Neuropathological abnormalities in AIDS patients have been associated with perivascular HIV-infected macrophages, gliosis, and abnormalities in the permeability of the BBB. The processes by which HIV causes these pathological conditions are not well understood. To characterize the mechanism by which HIV-1 Tat protein modulates human brain microvascular endothelial cell (HBMEC) functions, we studied the effects of HIV-1 Tat in modulating HBMEC apoptosis and permeability. Treatment of HBMEC with HIV-1 Tat led to Flk-1/KDR and Flt-4 receptor activation and the release of NO. The protein levels of endothelial NO synthase (NOS) and inducible NOS were increased by HIV-1 Tat stimulation. Importantly, HIV-1 Tat caused apoptosis of HBMEC, as evidenced by changes in the cleavage of poly(A)DP-ribose polymerase, DNA laddering, and incorporation of fluorescein into the nicked chromosomal DNA (TUNEL assay). HIV-1 Tat-mediated apoptosis in HBMEC was significantly inhibited in the presence of N-nitro-L-arginine methyl ester (an inhibitor of NOS) and wortmannin (a phosphoinositol 3-kinase inhibitor). Furthermore, HIV-1 Tat treatment significantly increased HBMEC permeability, and pretreatment with both N-nitro-L-arginine methyl ester and wortmannin inhibited the Tat-induced permeability. Taken together, these results indicate that dysregulated production of NO by HIV-1 Tat plays a pivotal role in brain endothelial injury, resulting in the irreversible loss of BBB integrity, which may lead to enhanced infiltration of virus-carrying cells across the BBB.




This article has been cited by other articles:


Home page
 J. Virol.Home page
L.-W. Qian, W. Greene, F. Ye, and S.-J. Gao
Kaposi's Sarcoma-Associated Herpesvirus Disrupts Adherens Junctions and Increases Endothelial Permeability by Inducing Degradation of VE-Cadherin
J. Virol., December 1, 2008; 82(23): 11902 - 11912.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Gupta, R. Boppana, G. C. Mishra, B. Saha, and D. Mitra
HIV-1 Tat Suppresses gp120-Specific T Cell Response in IL-10-Dependent Manner
J. Immunol., January 1, 2008; 180(1): 79 - 88.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
J. Rumbaugh, J. Turchan-Cholewo, D. Galey, C. St. Hillaire, C. Anderson, K. Conant, and A. Nath
Interaction of HIV Tat and matrix metalloproteinase in HIV neuropathogenesis: a new host defense mechanism
FASEB J, August 1, 2006; 20(10): 1736 - 1738.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
X. Zhang, J. F. Wang, B. Chandran, K. Persaud, B. Pytowski, J. Fingeroth, and J. E. Groopman
Kaposi's Sarcoma-associated Herpesvirus Activation of Vascular Endothelial Growth Factor Receptor 3 Alters Endothelial Function and Enhances Infection
J. Biol. Chem., July 15, 2005; 280(28): 26216 - 26224.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
E. A. Acheampong, Z. Parveen, L. W. Muthoga, M. Kalayeh, M. Mukhtar, and R. J. Pomerantz
Human Immunodeficiency Virus Type 1 Nef Potently Induces Apoptosis in Primary Human Brain Microvascular Endothelial Cells via the Activation of Caspases
J. Virol., April 1, 2005; 79(7): 4257 - 4269.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
F. Walker, H. Adle-Biassette, P. Madelenat, D. Henin, and T. Lehy
Increased Apoptosis in Cervical Intraepithelial Neoplasia Associated with HIV Infection: Implication of Oncogenic Human Papillomavirus, Caspases, and Langerhans Cells
Clin. Cancer Res., April 1, 2005; 11(7): 2451 - 2458.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Agbottah, C. de La Fuente, S. Nekhai, A. Barnett, A. Gianella-Borradori, A. Pumfery, and F. Kashanchi
Antiviral Activity of CYC202 in HIV-1-infected Cells
J. Biol. Chem., January 28, 2005; 280(4): 3029 - 3042.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
M. D. Bobardt, P. Salmon, L. Wang, J. D. Esko, D. Gabuzda, M. Fiala, D. Trono, B. Van der Schueren, G. David, and P. A. Gallay
Contribution of Proteoglycans to Human Immunodeficiency Virus Type 1 Brain Invasion
J. Virol., June 15, 2004; 78(12): 6567 - 6584.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
J. Stebbing, B. Gazzard, and D. C. Douek
Where Does HIV Live?
N. Engl. J. Med., April 29, 2004; 350(18): 1872 - 1880.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2003 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2003 by The American Association of Immunologists, Inc. All rights reserved.