Homer1a attenuates glutamate-induced oxidative injury in HT-22 cells through regulation of store-operated calcium entry.
Calcium disequilibrium is extensively involved in oxidative stress-induced neuronal injury. Although Homer1a is known to regulate several neuronal calcium pathways, its effects on, or its exact relationship with, oxidative stress-induced neuronal injury has not yet been fully elucidated. We found that Homer1a protected HT-22 cells from glutamate-induced oxidative stress injury by inhibiting final-phase intracellular calcium overload and mitochondrial oxidative stress. In these cells, stromal interactive molecule 1 (STIM1) puncta, but not the protein level, was significantly increased after glutamate treatment. Store-operated calcium entry (SOCE) inhibitors and cells in which a key component of SOCE (STIM1) was knocked out were used as glutamate-induced oxidative stress injury models. Both models demonstrated significant improvement of HT-22 cell survival after glutamate treatment. Additionally, increased Homer1a protein levels significantly inhibited SOCE and decreased the association of STIM1-Orai1 triggered by glutamate. These results suggest that up-regulation of Homer1a can protect HT-22 cells from glutamate-induced oxidative injury by disrupting the STIM1-Oria1 association, and then by inhibiting the SOCE-mediated final-phrase calcium overload. Thus, regulation of Homer1a, either alone or in conjunction with SOCE inhibition, may serve as key therapeutic interventional targets for neurological diseases in which oxidative stress is involved in the etiology or progression of the disease.
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, P. R. China.
Wei
W
Rao
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, P. R. China.
Cheng
C
Peng
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, P. R. China.
Lei
L
Zhang
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, P. R. China.|Department of Radiotherapy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, P. R. China.
Ning
N
Su
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, P. R. China.
Kai
K
Wang
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, P. R. China.
Hao
H
Hui
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, P. R. China.
Shu-Hui
SH
Dai
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, P. R. China.
Yue-Fan
YF
Yang
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, P. R. China.
Peng
P
Luo
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, P. R. China.
Zhou
Z
Fei
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