Propofol inhibits caspase-3 in astroglial cells: role of heme oxygenase-1.
Several lines of evidence have extensively demonstrated that peroxynitrite plays a pivotal role in Central Nervous System (CNS) injuries. The present study was aimed at elucidating the molecular mechanism by which propofol attenuates peroxynitrite-mediated injury in the brain. Primary cultured astroglial cells were incubated for 18 h with a known peroxynitrite donor (SIN-1,3 mM) in the presence or absence of propofol (40 microM, 80 microM and 160 microM). The protective effects of propofol were evaluated by MTT cytotoxicity assay, LDH release, and caspase-3 activation by Western blot analysis. Appropriate propofol concentrations (ranging from 40 microM to 160 microM) significantly increased HO-1 expression and attenuated SIN-1-mediated cytotoxicity and caspase-3 activation. The protective effects of propofol were mitigated by the addition of tin-mesoporphirin (SnMP), a potent inhibitor of HO activity. The addition of a specific synthetic inhibitor of NF-kappaB abolished propofol-mediated HO-1 induction, suggesting a possible role for this nuclear transcriptional factor in our experimental conditions. These findings indicate that propofol attenuates peroxynitrite-mediated apoptosis in astroglial cells, a property that may be relevant in both physiological and pathological processes in the CNS.
Acquaviva
Rosaria
R
Department of Biological Chemistry, Medical Chemistry and Molecular Biology, University of Catania, Italy.
Campisi
Agata
A
Raciti
Giuseppina
G
Avola
Roberto
R
Barcellona
Maria Luisa
ML
Vanella
Luca
L
Li Volti
Giovanni
G
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology*; D015153:Blotting, Western; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D030421:Peroxynitrous Acid / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D061945:Caspase Inhibitors; D020030:Nitric Oxide Donors; D030421:Peroxynitrous Acid; C002385:linsidomine; D008981:Molsidomine; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D015742:Propofol