HIV-1 gp120-induced apoptosis in the rat neocortex involves enhanced expression of cyclo-oxygenase type 2 (COX-2).
The effect of subchronic intracerebroventricular (i.c.v.) injection of the human immunodeficiency virus type 1 (HIV-1) recombinant protein gp120 (100 ng, given daily for up to 7 consecutive days) on cyclooxygenase type 2 (COX-2) expression was studied by immunohistochemistry in the brain of adult rats. In comparison to control, bovine serum albumin (100 ng, given i.c.v. for up to 7 days) treated animals (n = 6), a single daily injection of the viral protein for 7 consecutive days enhanced the number of COX-2 immunoreactive cells in the brain cortex of rats (n = 6 per group) and this was accompanied by a 50% increase over control PGE2 content in whole brain tissue homogenates (n = 6). In another series of experiments, pretreatment of rats (n = 6) with indomethacin (6.0 mg/kg given i.p. 1 h before gp120 injection), an inhibitor COX activity, prevented apoptotic death typically produced by gp120 in the neocortex of rat suggesting that enhancement of COX-2 expression may be involved in the mechanisms of apoptosis yielded by the HIV-1 coat protein.
Bagetta
G
G
Department of Pharmaco-Biology, University of Calabria at Cosenza, Italy. Bagetta@mail.csdim.unical.it
Corasaniti
M T
MT
Paoletti
A M
AM
Berliocchi
L
L
Nisticò
R
R
Giammarioli
A M
AM
Malorni
W
W
Finazzi-Agrò
A
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D015232:Dinoprostone / Q000032:analysis; D015699:HIV Envelope Protein gp120 / Q000633:toxicity*; D015497:HIV-1; D007213:Indomethacin / Q000494:pharmacology; D007276:Injections, Intraventricular; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D019579:Neocortex / Q000187:drug effects* / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015699:HIV Envelope Protein gp120; D007527:Isoenzymes; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D007213:Indomethacin