Peroxynitrite decomposition catalyst prevents apoptotic cell death in a human astrocytoma cell line incubated with supernatants of HIV-infected macrophages.
BACKGROUND
Oxidative stress has shown to contribute in the mechanisms underlying apoptotic cell death occurring in AIDS-dementia complex. Here we investigated the role of peroxynitrite in apoptosis occurring in astroglial cells incubated with supernatants of HIV-infected human primary macrophages (M/M).


RESULTS
Flow cytometric analysis (FACS) of human cultured astrocytes shortly incubated with HIV-1-infected M/M supernatants showed apoptotic cell death, an effect accompanied by pronounced staining for nitrotyrosine (footprint of peroxynitrite) and by abnormal formation of malondialdehyde (MDA). Pretreatment of astrocytes with the peroxynitrite decomposition catalyst FeTMPS antagonized HIV-related astrocytic apoptosis, MDA formation and nitrotyrosine staining.


CONCLUSIONS
Taken together, our results suggest that inhibition of peroxynitrite leads to protection against peroxidative stress accompanying HIV-related apoptosis of astrocytes. Overall results support the role of peroxynitrite in HIV-related programmed death of astrocytes and suggest the use of peroxynitrite decomposition catalyst to counteract HIV-1-related neurological disorders.
Muscoli
Carolina
C
Faculty of Pharmacy, University of Catanzaro Magna Graecia, Roccelletta di Borgia, Catanzaro, Italy. muscoli@uniroma3.it
Salvemini
Daniela
D
Paolino
Donatella
D
Iannone
Michelangelo
M
Palma
Ernesto
E
Cufari
Antonio
A
Rotiroti
Domenicantonio
D
Perno
Carlo Federico
CF
Aquaro
Stefano
S
Mollace
Vincenzo
V
D017209:Apoptosis / Q000187:drug effects; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001254:Astrocytoma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002384:Catalysis; D017077:Culture Media, Conditioned / Q000633:toxicity*; D005290:Ferric Compounds / Q000494:pharmacology*; D005434:Flow Cytometry; D015658:HIV Infections; D015497:HIV-1; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D008315:Malondialdehyde / Q000032:analysis / Q000378:metabolism; D008665:Metalloporphyrins / Q000494:pharmacology*; D030421:Peroxynitrous Acid / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism
C112917:5,10,15,20-tetrakis(2,4,6-trimethyl-3,3-disulfonatophenyl)porphyrinato iron(III); D017077:Culture Media, Conditioned; D005290:Ferric Compounds; D008665:Metalloporphyrins; D030421:Peroxynitrous Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde