title: Knockdown of STIM1 improves neuronal survival after traumatic neuronal injury through regulating mGluR1-dependent Ca(2+) signaling in mouse cortical neurons.
abstract: Activation of glutamate receptors and followed increase of intracellular calcium concentration is a key pathological mechanism involved in secondary neuronal injury after traumatic brain injury (TBI). Stromal interaction molecule (STIM) proteins are considered to be important players in regulating neuronal Ca(2+) homeostasis under normal aging and pathological conditions. Here, we investigated the role of STIM1 in regulating metabotropic glutamate receptor 1 (mGluR1)-related Ca(2+) signaling and neuronal survival by using an in vitro traumatic neuronal injury (TNI) model. The expression of STIM1 was significantly increased at both mRNA and protein levels after TNI. Down-regulation of STIM1 by specific small interfere RNA significantly preserved neuronal viability, decreased lactate dehydrogenase release, and inhibited apoptotic cell death after traumatic injury. Moreover, knockdown of STIM1 significantly alleviated the mGluR1-related increase of cytoplasmic Ca(2+) levels after TNI. By analyzing Ca(2+) imaging in Ca(2+)-free conditions, we demonstrated that the mGluR1-dependent inositol trisphosphate receptor and/or ryanodine receptor-mediated Ca(2+) release from the endoplasmic reticulum after TNI is strongly attenuated in the absence of STIM1. Together, our results demonstrate that in the mammalian nervous system, STIM1 is a key regulator of mGluR1-dependent Ca(2+) signaling and knockdown of STIM1 might be an effective intervention target in TBI.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Road, Xi'an, 710061, Shaanxi, China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Hou
authors.forename: Zhan-Hui
authors.initials: ZH
authors.lastname: Liu
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Wen-Jia
authors.initials: WJ
authors.lastname: Cheng
authors.forename: Shi-Wen
authors.initials: SW
authors.lastname: Guo
mesh_terms: D000818:Animals; D017209:Apoptosis; D015220:Calcium Channels / Q000378:metabolism*; D020013:Calcium Signaling; D002470:Cell Survival; D002540:Cerebral Cortex / Q000473:pathology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D055785:Gene Knockdown Techniques; D042541:Intracellular Space / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D000071737:Stromal Interaction Molecule 1
chemical_list: D015220:Calcium Channels; D018094:Receptors, Metabotropic Glutamate; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; C104077:metabotropic glutamate receptor type 1