title: Blockade of store-operated calcium entry alleviates high glucose-induced neurotoxicity via inhibiting apoptosis in rat neurons.
abstract: Altered store-operated calcium entry (SOCE) has been suggested to be involved in many diabetic complications. However, the association of altered SOCE and diabetic neuronal damage remains unclear. This study aimed to investigate the effects of altered SOCE on primary cultured rat neuron injury induced by high glucose. Our data demonstrated that high glucose increased rat neuron injury and upregulated the expression of store-operated calcium channel (SOC). Inhibition of SOCE by a pharmacological inhibitor and siRNA knockdown of stromal interaction molecule 1 weakened the intracellular calcium overload, restored mitochondrial membrane potential, downregulated cytochrome C release and inhibited cell apoptosis. As well, treatment with the calcium chelator BAPTA-AM prevented cell apoptosis by ameliorating the high glucose-increased intracellular calcium level. These findings suggest that SOCE blockade may alleviate high glucose-induced neuronal damage by inhibiting apoptosis. SOCE might be a promising therapeutic target in diabetic neurotoxicity.
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Brain Science Research Institute of Shandong University, Jinan, Shandong Province 250012, PR China. Electronic address: kuankuancui@163.com.
authors.forename: Zhenkuan
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Brain Science Research Institute of Shandong University, Jinan, Shandong Province 250012, PR China. Electronic address: xuwenzhe2008@126.com.
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Brain Science Research Institute of Shandong University, Jinan, Shandong Province 250012, PR China. Electronic address: super326@126.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Brain Science Research Institute of Shandong University, Jinan, Shandong Province 250012, PR China. Electronic address: zhangbin747@126.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Brain Science Research Institute of Shandong University, Jinan, Shandong Province 250012, PR China. Electronic address: feng.li@hotmail.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Qilu Hospital of Shandong University, Brain Science Research Institute of Shandong University, Jinan, Shandong Province 250012, PR China. Electronic address: ns3000@126.com.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000166:cytology; D005434:Flow Cytometry; D005947:Glucose / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D000071737:Stromal Interaction Molecule 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D034741:RNA, Small Interfering; C518857:Stim1 protein, rat; D000071737:Stromal Interaction Molecule 1; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D045304:Cytochromes c; D005947:Glucose; D002118:Calcium
keywords: Apoptosis; High glucose; Neurotoxicity; Store-operated calcium entry; Stromal interaction molecule