HIV-1 Tat neurotoxicity: A model of acute and chronic exposure, and neuroprotection by gene delivery of antioxidant enzymes

被引:54
作者
Agrawal, Lokesh [1 ]
Louboutin, Jean-Pierre [1 ]
Reyes, Beverly A. S. [2 ]
Van Bockstaele, Elisabeth J. [2 ]
Strayer, David S. [1 ]
机构
[1] Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA
[2] Thomas Jefferson Univ, Farber Inst Neurosci, Dept Neurosurg, Philadelphia, PA 19107 USA
关键词
HIV-1; Tat; Antioxidant enzymes; Gene therapy; SOD1; HIV-1 associated neurocognitive disorders; CENTRAL-NERVOUS-SYSTEM; METHYL-D-ASPARTATE; OXIDATIVE STRESS; IN-VIVO; GLUTATHIONE-PEROXIDASE; ENVELOPE GLYCOPROTEIN; RECOMBINANT SV40; PROTECT NEURONS; RAT MODEL; VIRUS;
D O I
10.1016/j.nbd.2011.10.005
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
HIV-associated neurocognitive disorder (HAND) is an increasingly common, progressive disease characterized by neuronal loss and progressively deteriorating CNS function. HIV-1 gene products, particularly gp120 and Tat elicit reactive oxygen species (ROS) that lead to oxidant injury and cause neuron apoptosis. Understanding of, and developing therapies for, HAND requires accessible models of the disease. We have devised experimental approaches to studying the acute and chronic effects of Tat on the CNS. We studied acute exposure by injecting recombinant Tat protein into the caudate-putamen (CP). Ongoing Tat expression, which more closely mimics HIV-1 infection of the brain, was studied by delivering Tat-expression over time using an SV40-derived gene delivery vector, SV(Tat). Both acute and chronic Tat exposure induced lipid peroxidation and neuronal apoptosis. Finally, prior administration of recombinant SV40 vectors carrying antioxidant enzymes, copper/zinc superoxide dismutase (SOD1) or glutathione peroxidase (GPx1), protected from Tat-induced apoptosis and oxidative injury. Thus, injection of recombinant HIV-1 Tat and the expression vector, SV(Tat), into the rat CP cause respectively acute or ongoing apoptosis and oxidative stress in neurons and may represent useful animal models for studying the pathogenesis and, potentially, treatment of HIV-1 Tat-related damage. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:657 / 670
页数:14
相关论文
共 91 条
[1]   Antioxidant enzyme gene delivery to protect from HIV-1 gp120-induced neuronal apoptosis [J].
Agrawal, L. ;
Louboutin, J-P ;
Reyes, B. A. S. ;
Van Bockstaele, E. J. ;
Strayer, D. S. .
GENE THERAPY, 2006, 13 (23) :1645-1656
[2]   Preventing HIV-1 tat-induced neuronal apoptosis using antioxidant enzymes: Mechanistic and therapeutic implications [J].
Agrawal, Lokesh ;
Louboutin, Jean-Pierre ;
Strayer, David S. .
VIROLOGY, 2007, 363 (02) :462-472
[3]   Temporal relationships between HIV-1 Tat-induced neuronal degeneration, OX-42 immunoreactivity, reactive astrocytosis, and protein oxidation in the rat striatum [J].
Aksenov, MY ;
Hasselrot, U ;
Wu, GH ;
Nath, A ;
Anderson, C ;
Mactutus, CF ;
Booze, RM .
BRAIN RESEARCH, 2003, 987 (01) :1-9
[4]   Oxidative damage induced by the injection of HIV-1 Tat protein in the rat striatum [J].
Aksenov, MY ;
Hasselrot, U ;
Bansal, AK ;
Wu, GH ;
Nath, A ;
Anderson, C ;
Mactutus, CF ;
Booze, RM .
NEUROSCIENCE LETTERS, 2001, 305 (01) :5-8
[5]   Dementia and neurocognitive disorders due to HIV-1 infection [J].
Ances, Beau M. ;
Ellis, Ronald J. .
SEMINARS IN NEUROLOGY, 2007, 27 (01) :86-92
[6]   Oxidative stress in neurodegeneration: cause or consequence? [J].
Andersen, JK .
NATURE MEDICINE, 2004, 10 (07) :S18-S25
[7]   Updated research nosology for HIV-associated neurocognitive disorders [J].
Antinori, A. ;
Arendt, G. ;
Becker, J. T. ;
Brew, B. J. ;
Byrd, D. A. ;
Cherner, M. ;
Clifford, D. B. ;
Cinque, P. ;
Epstein, L. G. ;
Goodkin, K. ;
Gisslen, M. ;
Grant, I. ;
Heaton, R. K. ;
Joseph, J. ;
Marder, K. ;
Marra, C. M. ;
McArthur, J. C. ;
Nunn, M. ;
Price, R. W. ;
Pulliam, L. ;
Robertson, K. R. ;
Sacktor, N. ;
Valcour, V. ;
Wojna, V. E. .
NEUROLOGY, 2007, 69 (18) :1789-1799
[8]   SCID mice with HIV encephalitis develop behavioral abnormalities [J].
Avgeropoulos, N ;
Kelley, B ;
Middaugh, L ;
Arrigo, S ;
Persidsky, Y ;
Gendelman, HE ;
Tyor, WR .
JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY, 1998, 18 (01) :13-20
[9]   Axonal transport of human immunodeficiency virus type 1 envelope protein glycoprotein 120 is found in association with neuronal apoptosis [J].
Bachis, Alessia ;
Aden, Sadia A. ;
Nosheny, Rachel L. ;
Andrews, Peter M. ;
Mocchetti, Italo .
JOURNAL OF NEUROSCIENCE, 2006, 26 (25) :6771-6780
[10]   HIV proteins (gp120 and Tat) and methamphetamine in oxidative stress-induced damage in the brain: Potential role of the thiol antioxidant N-acetylcysteine amide [J].
Banerjee, Atrayee ;
Zhang, Xinsheng ;
Manda, Kalyan Reddy ;
Banks, William A. ;
Ercal, Nuran .
FREE RADICAL BIOLOGY AND MEDICINE, 2010, 48 (10) :1388-1398