Propofol Inhibits Caspase-3 in Astroglial Cells: Role of Heme Oxygenase-1

Author(s): Rosaria Acquaviva, Agata Campisi, Giuseppina Raciti, Roberto Avola, Maria Luisa Barcellona, Luca Vanella, Giovanni Li Volti.

Journal Name: Current Neurovascular Research

Volume 2 , Issue 2 , 2005

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Abstract:

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 μM) in the presence or absence of propofol (40 μM, 80 mM and 160 μM). 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 μM to 160 μM) 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-κB 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 peroxynitritemediated apoptosis in astroglial cells, a property that may be relevant in both physiological and pathological processes in the CNS.

Keywords: heme oxygenase, peroxynitrite, astrocytes, apoptosis, propofol, caspase-3

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Article Details

VOLUME: 2
ISSUE: 2
Year: 2005
Page: [141 - 148]
Pages: 8
DOI: 10.2174/1567202053586820
Price: $58

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