PMID- 29241198
OWN - NLM
STAT- MEDLINE
DCOM- 20180314
LR  - 20190212
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 44
IP  - 5
DP  - 2017
TI  - FAM3A Protects Against Glutamate-Induced Toxicity by Preserving Calcium 
      Homeostasis in Differentiated PC12 Cells.
PG  - 2029-2041
LID - 10.1159/000485943 [doi]
AB  - BACKGROUND/AIMS: Stroke is the leading cause of adult disability, and 
      glutamate-induced dysregulation of intracellular Ca2+ homeostasis is a key 
      mechanism. FAM3A is the first member of the family with sequence similarity 3 
      (FAM3) gene family, and its biological function remains largely unknown. We have 
      recently reported that FAM3A exerts protective effects against oxidative stress 
      and mitochondrial dysfunction in HT22 cells. METHODS: Here, we investigated the 
      protective effects of FAM3A using a glutamate-induced neuronal injury model in 
      nerve growth factor (NGF)-differentiated PC12 cells. The protective effects were 
      determined by measuring lactate dehydrogenase (LDH) release, apoptosis and 
      mitochondrial oxidative stress. Ca2+ imaging was performed to detect changes in 
      intracellular Ca2+ concentration in PC12 cells. The related molecular mechanisms 
      were investigated by fluorescence staining, coimmunoprecipitation (Co-IP) and 
      western blotting. RESULTS: Upregulation of FAM3A by lentivirus transfection 
      markedly decreased LDH release, inhibited apoptosis and reduced mitochondrial 
      oxidative stress, which were accompanied by alleviated intracellular Ca2+ levels 
      as measured by calcium imaging. The results of western blotting showed that FAM3A 
      significantly decreased the surface expression of metabotropic glutamate receptor 
      1/5 (mGluR1/5), with no effect on the expression of N-methyl-d-aspartic acid 
      receptor (NMDAR) or alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid 
      receptor (AMPAR) subunits. FAM3A overexpression also inhibited the intracellular 
      Ca2+ release mediated by mGluR1/5 and inositol 1,4,5-trisphosphate receptor 
      (IP3R), but not the ryanodine receptor (RyR). In addition, FAM3A significantly 
      attenuated the store-operated calcium entry (SOCE) induced by thapsigargin (Tg), 
      but the expression of SOCE-related proteins was not altered. The results of 
      coimmunoprecipitation (Co-IP) showed that FAM3A disrupted the interaction of 
      stromal interaction molecule 1 (STIM1) with Orai1 triggered by glutamate. 
      CONCLUSION: These results suggest that the upregulation of FAM3A protects against 
      glutamate-induced dysfunction of Ca2+ homeostasis not only by inhibiting 
      mGluR1/5-dependent endoplasmic reticulum (ER) Ca2+ release, but also by 
      attenuating SOCE mediated by the STIM1-Orai1 interaction.
CI  - (c) 2017 The Author(s). Published by S. Karger AG, Basel.
FAU - Song, Qing
AU  - Song Q
FAU - Gou, Wen-Li
AU  - Gou WL
FAU - Zou, Yu-Liang
AU  - Zou YL
LA  - eng
PT  - Journal Article
DEP - 20171212
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Cytokines)
RN  - 0 (FAM3A protein, rat)
RN  - 0 (Inositol 1,4,5-Trisphosphate Receptors)
RN  - 0 (ORAI1 Protein)
RN  - 0 (Protective Agents)
RN  - 0 (Receptor, Metabotropic Glutamate 5)
RN  - 0 (Receptors, Metabotropic Glutamate)
RN  - 0 (Stromal Interaction Molecule 1)
RN  - 0 (Stromal Interaction Molecule 2)
RN  - 0 (metabotropic glutamate receptor type 1)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 67526-95-8 (Thapsigargin)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Calcium/*metabolism
MH  - Cell Differentiation/*drug effects
MH  - Cytokines/genetics/*metabolism
MH  - Genetic Vectors/genetics/metabolism
MH  - Glutamic Acid/*toxicity
MH  - Inositol 1,4,5-Trisphosphate Receptors/metabolism
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Nerve Growth Factor/pharmacology
MH  - ORAI1 Protein/genetics/metabolism
MH  - Oxidative Stress
MH  - PC12 Cells
MH  - Protective Agents/*pharmacology
MH  - Rats
MH  - Receptor, Metabotropic Glutamate 5/metabolism
MH  - Receptors, Metabotropic Glutamate/metabolism
MH  - Stromal Interaction Molecule 1/genetics/metabolism
MH  - Stromal Interaction Molecule 2/genetics/metabolism
MH  - Thapsigargin/pharmacology
OTO - NOTNLM
OT  - Calcium homeostasis
OT  - Fam3a
OT  - Glutamate receptors
OT  - Mitochondrial dysfunction
OT  - SOCE
EDAT- 2017/12/15 06:00
MHDA- 2018/03/15 06:00
CRDT- 2017/12/15 06:00
PHST- 2017/06/09 00:00 [received]
PHST- 2017/11/17 00:00 [accepted]
PHST- 2017/12/15 06:00 [pubmed]
PHST- 2018/03/15 06:00 [medline]
PHST- 2017/12/15 06:00 [entrez]
AID - 000485943 [pii]
AID - 10.1159/000485943 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2017;44(5):2029-2041. doi: 10.1159/000485943. Epub 2017 Dec 
      12.