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STIM1 restores calcium influx and protects neurons against ER stress and cell death (663.1)
Author(s) -
Zhang Changfeng,
Thomas David
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.663.1
Subject(s) - thapsigargin , endoplasmic reticulum , microbiology and biotechnology , neuroprotection , stim1 , unfolded protein response , chemistry , calcium signaling , signal transduction , biology , neuroscience
We have used the unique Ca signaling neuronal cell line NG115‐401L (401L) to test the hypothesis that the pivotal Ca influx channel regulator protein STIM1 participates in the control of endoplasmic reticulum (ER) Ca store integrity, serving as an important mediator of neuroprotection. 40lL neurons are a useful cell model for these investigations given the native lack of STIM1 expression, in a background phenotype with well characterized perturbations in ER Ca regulation and control of Ca influx pathways. We tested global Ca signaling responses in STIM1 restored 401L neurons observing, as has been reported previously, that expression of STIM1 by itself reconstitutes thapsigargin (TG)‐evoked Ca influx. Indeed, we found in general that mere expession of STIM1 in the 401L cell could significantly augment Ca influx induced by hormone/neurotransmitter coupled phosphatidylinositol (PI)‐linked receptor pathways. Significantly, in addition to restoration of robust Ca influx responses, expression of STIM1 in 401L cells conferred a neuroprotective response to the potent actions of TG‐induced ER perturbation and cell death. Moreover, STIM1 expression also protected 401L cells from oxidative damage induced by glutathione depletion. We suggest that the absence of STIM1 expression in these neurons produces ER stress with partially depleted Ca stores and a high sensitivity to ER perturbation and oxidative stress.