Antioxidants: promising neuroprotection against cardiotoxin-4b-induced cell death which triggers oxidative stress with early calpain activation.
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 4h 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.
Toh
Tan Boon
TB
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore.
Chen
Minghui Jessica
MJ
Armugam
Arunmozhiarasi
A
Peng
Zhao Feng
ZF
Li
Qiu-Tian
QT
Jeyaseelan
Kandiah
K
Cheung
Nam Sang
NS
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002154:Calpain / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004179:Cobra Cardiotoxin Proteins; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
D000975:Antioxidants; D004179:Cobra Cardiotoxin Proteins; D004546:Elapid Venoms; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D002154:Calpain