Evidence that increases of mitochondrial immunoreactive IL-1beta by HIV-1 gp120 implicate in situ cleavage of pro-IL-1beta in the neocortex of rat.
Immunoelectron microscopy analysis of brain tissue sections and rat-specific sandwich ELISA allowed the localization of interleukin-1beta (IL-1beta) immunoreactivity in the mitochondria and cytosol of neocortical tissue preparations from the brain of naive, untreated, rats and rats receiving a single daily injection into one lateral cerebral ventricle (i.c.v.) of bovine serum albumin (BSA; 100 ng/day) for seven consecutive days. Interestingly, seven days i.c.v. treatment with the HIV-1 coat protein gp120 (100 ng/day) enhances IL-1beta immunoreactivity in the cellular fractions studied. Elevation of mitochondrial immunoreactive IL-1beta levels seems to originate from the conversion operated by the interleukin converting enzyme (ICE) of mitochondrial pro-IL-1beta; in fact, IL-1beta increases reported in the ELISA experiments were paralleled by a decrease of the mitochondrial pro-IL-1beta 31-kDa band in conjunction with enhanced expression of the p20 component of activated ICE. In conclusion, the present results demonstrate that gp120-enhanced neocortical expression of IL-1beta originates, at least in part, from in situ cleavage of mitochondrial pro-IL-1beta and suggest that this, together with the central role of the mitochondrion in the expression of programmed cell death, may be important for apoptosis induced by the viral coat protein in the brain of rats.
Corasaniti
M T
MT
Department of Pharmacological Sciences, Faculty of Pharmacy, Catanzaro, Italy.
Turano
P
P
Bilotta
A
A
Malorni
W
W
Stringaro
A R
AR
Nisticò
R
R
Finazzi-Agró
A
A
Bagetta
G
G
D000818:Animals; D001923:Brain Chemistry; D020170:Caspase 1 / Q000378:metabolism; D002458:Cell Fractionation; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007375:Interleukin-1 / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000008:administration & dosage
D015699:HIV Envelope Protein gp120; D007375:Interleukin-1; D011498:Protein Precursors; D012710:Serum Albumin, Bovine; D020170:Caspase 1