Effect of Huwentoxin-I on the Fas and TNF apoptosis pathway in the hippocampus of rat with global cerebral ischemia.
Neuronal injury is the most important reason for various brain injuries. Cytosolic Ca(2+) overloading has been proposed as one of the main cellular processes leading to neuronal death during cerebral ischemia. It is well accepted that Ca(2+) channel blockers can protect cerebral neurons from ischemic injury. In the present studies, we investigated the molecular mechanism for the neuro-protective effect of Huwentoxin-I (HWTX-I), a spider toxin selectively blocking N-type voltage-dependent Ca((2+)) channel, on rat models with global cerebral ischemia-reperfusion injury. Our studies demonstrated that HWTX-I could maintain the morphological stability of pyramidal cells in this model. Furthermore, HWTX-I could decrease the concentration of malon-dialdehyde, but increase the activity of superoxide dismutase and glutathione peroxidase. It also reduced the expression level of related factors of Fas and tumor necrosis factor death receptor apoptosis pathways in the hippocampus. In summary, HWTX-I has an obvious neuroprotective effect, which may act through its inhibition on a certain apoptosis pathway.
Wang
Yi-Rong
YR
Hunan Sports Vocational College, Changsha, Hunan 410014, PR China. douzi99@163.com
Liu
Ren-Yi
RY
Wang
Liang-Chun
LC
Mao
Hai-Feng
HF
Chen
Jia-Qin
JQ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects*; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D030162:Reptilian Proteins / Q000494:pharmacology*; D013111:Spider Venoms / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D053199:TNF Receptor-Associated Death Domain Protein / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology*
D018696:Neuroprotective Agents; D012333:RNA, Messenger; D030162:Reptilian Proteins; D013111:Spider Venoms; D053199:TNF Receptor-Associated Death Domain Protein; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; C083624:huwentoxin I; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D002118:Calcium