Evidence that the HIV-1 coat protein gp120 causes neuronal apoptosis in the neocortex of rat via a mechanism involving CXCR4 chemokine receptor.
The HIV-1 coat protein, gp120 (100 ng given intracerebroventricularly (i.c.v.) daily for seven consecutive days) causes DNA fragmentation in the brain neocortex of rat. In neocortical cells bearing ultrastructural features typical of apoptosis, electron microscopy revealed specific immunopositivity for neurofilament cytoskeletal proteins, suggesting the neuronal nature of dying cells. Neuronal apoptosis by gp120 implicates CXCR4 chemokine receptors; in fact, in rats receiving a single daily, non-neurotoxic, dose of SDF-1alpha (0.25 pmoles given i.c.v. for 7 days before gp120), the natural ligand of CXCR4 receptor, apoptosis was significantly hindered. The mechanism of SDF-1alpha protection involves inhibition of gp120-enhanced expression of IL-1beta, a cytokine implicated in the mechanisms of apoptosis induced by the viral protein in the neocortex of rat.
Corasaniti
M T
MT
Department of Pharmacobiological Sciences, University of Catanzaro Magna Graecia and IBAF-CNR, Catanzaro, Italy.
Piccirilli
S
S
Paoletti
A
A
Nisticò
R
R
Stringaro
A
A
Malorni
W
W
Finazzi-Agrò
A
A
Bagetta
G
G
D015526:AIDS Dementia Complex / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000276:immunology / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000494:pharmacology*; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008854:Microscopy, Electron; D019579:Neocortex / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D009498:Neurotoxins / Q000276:immunology / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D005904:Glial Fibrillary Acidic Protein; D015699:HIV Envelope Protein gp120; D007375:Interleukin-1; D016900:Neurofilament Proteins; D009498:Neurotoxins; D019718:Receptors, CXCR4