Cardiotoxin-4b (CTX-4b), isolated from Naja naja sputatrix venom, shows lethality in several cell types. Employing murine primary cortical neurons, this study was undertaken to investigate the molecular mechanisms of CTX-4b in the induction of neuronal death. CTX-4b induced a dose- and time-dependent neuronal death. Strong induction of calpains as early as 4 h post-CTX-4b 75 nM treatment was detected in neurons with negligible caspase 3 activation. For the first time in cultured murine primary cortical neurons, it was noted that CTX-4b-mediated cell death triggered oxidative stress with an increase in reactive oxygen species (ROS) levels, and that application of antioxidants showed effective attenuation of cell death. Taken together, these results indicate that CTX-4b-mediated neuronal death is associated with (i) early calpain activation and (ii) oxidative stress. Most importantly, antioxidants have proved to be a promising therapeutic avenue against CTX-4b-induced neuronal death.

Item Type:	Refereed Article
Research Division:	Biomedical and Clinical Sciences
Research Group:	Neurosciences
Research Field:	Cellular nervous system
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Clinical health not elsewhere classified
UTAS Author:	Cheung, NS (Dr Nam Cheung)
ID Code:	61648
Year Published:	2008
Web of Science® Times Cited:	5
Deposited By:	Menzies Institute for Medical Research
Deposited On:	2010-03-04
Last Modified:	2010-05-04
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