Mu-calpain mediates hippocampal neuron death in rats after lithium-pilocarpine-induced status epilepticus.
Status epilepticus (SE) is a severe clinical manifestation of epilepsy which causes brain damage. The pathological process and underlying mechanisms involved in the programmed cell death (PCD) are still not fully clear. In the current study, rats were induced SE by lithium-pilocarpine administration. Our data showed hippocampal neurons death appeared at 6h after SE and sustained for 7 days. By blotting the activation of mu-calpain and its specific cleavage of nonerythroid alpha-spectrin (alphaSpII) (145 kDa) was evident at 1 and 3 days after SE, which coincided with Bid activation, apoptosis inducing factor (AIF) translocation and cytochrome c release from mitochondria, whereas, activated caspase-3 and caspase-3-specific fragments of alphaSpII (120 kDa) predominantly appeared at 5 and 7 days after SE. Moreover, MDL-28170, a calpain inhibitor, partially rescued the neuron death and attenuated the expression of activated mu-calpain, cleavage of Bid (15 kDa), AIF translocation and cytochrome c release. Taken together, our study indicated that mu-calpain mediated hippocampal neuron PCD is prior to caspase-3 activation. It functioned via translocation of Bid, AIF and cytochrome c release.
Wang
Shuhua
S
Department of Neurology, Qilu Hospital, Medical School of Shandong University, Jinan 250012, China.
Wang
Shengjun
S
Shan
Peiyan
P
Song
Zhaofeng
Z
Dai
Tingjun
T
Wang
Rong
R
Chi
Zhaofu
Z
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D002154:Calpain / Q000494:pharmacology*; D016923:Cell Death / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010862:Pilocarpine / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013049:Spectrin / Q000378:metabolism; D013226:Status Epilepticus / Q000139:chemically induced* / Q000473:pathology
D014150:Antipsychotic Agents; D051033:Apoptosis Inducing Factor; D051023:BH3 Interacting Domain Death Agonist Protein; C494816:Bid protein, rat; D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D018721:Muscarinic Agonists; D010862:Pilocarpine; D013049:Spectrin; D045304:Cytochromes c; D008094:Lithium; D002154:Calpain; C449002:mu-calpain; C058076:calpain inhibitor III