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HIV-1 gp120 upregulates matrix metalloproteinases and their inhibitors in a rat model of HIV encephalopathy.
Eur J Neurosci. 2011 Dec; 34(12):2015-23.EJ

Abstract

Matrix metalloproteinases (MMPs) are implicated in diverse processes, such as neuroinflammation, leakiness of the blood-brain barrier (BBB) and direct cellular damage in neurodegenerative and other CNS diseases. Tissue destruction by MMPs is regulated by their endogenous tissue inhibitors (TIMPs). TIMPs prevent excessive MMP-related degradation of extracellular matrix components. In a rat model of human immunodeficiency virus (HIV)-related encephalopathy, we described MMP-2 and MMP-9 upregulation by HIV-1 envelope gp120, probably via gp120-induced reactive oxygen species. Antioxidant gene delivery blunted gp120-induced MMP production. We also studied the effect of gp120 on TIMP-1 and TIMP-2 production. TIMP-1 and TIMP-2 levels increased 6 h after gp120 injection into rat caudate-putamen (CP). TIMP-1 and TIMP-2 colocalized mainly with neurons (92 and 95%, respectively). By 24 h, expression of these protease inhibitors diverged, as TIMP-1 levels remained high but TIMP-2 subsided. Gene delivery of the antioxidant enzymes Cu/Zn superoxide dismutase or glutathione peroxidase into the CP before injecting gp120 there reduced levels of gp120-induced TIMP-1 and TIMP-2, recapitulating the effect of antioxidant enzymes on gp120-induced MMP-2 and MMP-9. A significant correlation was observed between MMP/TIMP upregulation and BBB leakiness. Thus, HIV-1 gp120 upregulated TIMP-1 and TIMP-2 in the CP. Prior antioxidant enzyme treatment mitigated production of these TIMPs, probably by reducing MMP expression.

Authors+Show Affiliations

Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA. jplouboutin@hotmail.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22092673

Citation

Louboutin, Jean-Pierre, et al. "HIV-1 Gp120 Upregulates Matrix Metalloproteinases and Their Inhibitors in a Rat Model of HIV Encephalopathy." The European Journal of Neuroscience, vol. 34, no. 12, 2011, pp. 2015-23.
Louboutin JP, Reyes BA, Agrawal L, et al. HIV-1 gp120 upregulates matrix metalloproteinases and their inhibitors in a rat model of HIV encephalopathy. Eur J Neurosci. 2011;34(12):2015-23.
Louboutin, J. P., Reyes, B. A., Agrawal, L., Van Bockstaele, E. J., & Strayer, D. S. (2011). HIV-1 gp120 upregulates matrix metalloproteinases and their inhibitors in a rat model of HIV encephalopathy. The European Journal of Neuroscience, 34(12), 2015-23. https://doi.org/10.1111/j.1460-9568.2011.07908.x
Louboutin JP, et al. HIV-1 Gp120 Upregulates Matrix Metalloproteinases and Their Inhibitors in a Rat Model of HIV Encephalopathy. Eur J Neurosci. 2011;34(12):2015-23. PubMed PMID: 22092673.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HIV-1 gp120 upregulates matrix metalloproteinases and their inhibitors in a rat model of HIV encephalopathy. AU - Louboutin,Jean-Pierre, AU - Reyes,Beverly A S, AU - Agrawal,Lokesh, AU - Van Bockstaele,Elisabeth J, AU - Strayer,David S, Y1 - 2011/11/17/ PY - 2011/11/19/entrez PY - 2011/11/19/pubmed PY - 2012/4/5/medline SP - 2015 EP - 23 JF - The European journal of neuroscience JO - Eur J Neurosci VL - 34 IS - 12 N2 - Matrix metalloproteinases (MMPs) are implicated in diverse processes, such as neuroinflammation, leakiness of the blood-brain barrier (BBB) and direct cellular damage in neurodegenerative and other CNS diseases. Tissue destruction by MMPs is regulated by their endogenous tissue inhibitors (TIMPs). TIMPs prevent excessive MMP-related degradation of extracellular matrix components. In a rat model of human immunodeficiency virus (HIV)-related encephalopathy, we described MMP-2 and MMP-9 upregulation by HIV-1 envelope gp120, probably via gp120-induced reactive oxygen species. Antioxidant gene delivery blunted gp120-induced MMP production. We also studied the effect of gp120 on TIMP-1 and TIMP-2 production. TIMP-1 and TIMP-2 levels increased 6 h after gp120 injection into rat caudate-putamen (CP). TIMP-1 and TIMP-2 colocalized mainly with neurons (92 and 95%, respectively). By 24 h, expression of these protease inhibitors diverged, as TIMP-1 levels remained high but TIMP-2 subsided. Gene delivery of the antioxidant enzymes Cu/Zn superoxide dismutase or glutathione peroxidase into the CP before injecting gp120 there reduced levels of gp120-induced TIMP-1 and TIMP-2, recapitulating the effect of antioxidant enzymes on gp120-induced MMP-2 and MMP-9. A significant correlation was observed between MMP/TIMP upregulation and BBB leakiness. Thus, HIV-1 gp120 upregulated TIMP-1 and TIMP-2 in the CP. Prior antioxidant enzyme treatment mitigated production of these TIMPs, probably by reducing MMP expression. SN - 1460-9568 UR - https://www.unboundmedicine.com/medline/citation/22092673/HIV_1_gp120_upregulates_matrix_metalloproteinases_and_their_inhibitors_in_a_rat_model_of_HIV_encephalopathy_ L2 - https://doi.org/10.1111/j.1460-9568.2011.07908.x DB - PRIME DP - Unbound Medicine ER -