PMID- 31545891
OWN - NLM
STAT- MEDLINE
DCOM- 20200904
LR  - 20200904
IS  - 1948-7193 (Electronic)
IS  - 1948-7193 (Linking)
VI  - 10
IP  - 10
DP  - 2019 Oct 16
TI  - Activation of G-Protein-Coupled Receptor 30 Protects Neurons against 
      Excitotoxicity through Inhibiting Excessive Autophagy Induced by Glutamate.
PG  - 4227-4236
LID - 10.1021/acschemneuro.9b00287 [doi]
AB  - Autophagy is a protecting intracellular pathway to transmit unnecessary or 
      dysfunctional components to the lysosome for degeneration. Autophagic imbalance 
      is connected with neurodegeneration. Neurodegenerative diseases including 
      Parkinson's disease, Alzheimer's disease, and Huntington's disease are closely 
      related to excitotoxicity and neuronal loss. Activation of G-protein-coupled 
      receptor 30 (GPR30), an estrogen membrane receptor, protects neurons from 
      excitotoxicity-induced cell death. However, whether autophagy is involved in the 
      neuroprotective effect of GPR30 activation is not well-known. In this study, 
      methyl thiazolyl tetrazolium (MTT), Western blot, monodansylcadaverine (MDC) 
      staining, and immunofluorescent staining were employed to detect the role of 
      autophagy in cultured primary cortical neurons after glutamate exposure and G1 
      treatment. Pretreatment of G1 (GPR30 specific agonist) reduced neuronal loss 
      through inhibiting excessive autophagy induced by glutamate exposure, which was 
      blocked by GPR30 antagonist G15, phosphatidylinositol-3-kinase (PI3K), and the 
      mammalian target of rapamycin (mTOR) inhibitors. These data suggest that GPR30 
      protects neurons from cell loss primarily by modulating PI3K-AKT-mTOR signaling 
      pathway. In addition, G1 alone did not affect the basal autophagy and cell 
      viability. We conclude that GPR30 activation reduces glutamate-induced excessive 
      autophagy in neurons and protects neurons against excitotoxicity.
FAU - Yue, Jiao
AU  - Yue J
AD  - Department of Pharmacology, School of Pharmacy , Fourth Military Medical 
      University , Xi'an 710032 , China.
AD  - State Key Laboratory of Military Stomatology, National Clinical Research Center 
      for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, 
      Department of Pharmacy, School of Stomatology , Fourth Military Medical 
      University , Xi'an 710032 , China.
FAU - Wang, Xin-Shang
AU  - Wang XS
AD  - Department of Pharmacology, School of Pharmacy , Fourth Military Medical 
      University , Xi'an 710032 , China.
FAU - Feng, Bin
AU  - Feng B
AD  - State Key Laboratory of Military Stomatology, National Clinical Research Center 
      for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, 
      Department of Pharmacy, School of Stomatology , Fourth Military Medical 
      University , Xi'an 710032 , China.
FAU - Hu, Li-Ning
AU  - Hu LN
AD  - Department of Pharmacology, School of Pharmacy , Fourth Military Medical 
      University , Xi'an 710032 , China.
FAU - Yang, Liu-Kun
AU  - Yang LK
AD  - Department of Pharmacology, School of Pharmacy , Fourth Military Medical 
      University , Xi'an 710032 , China.
FAU - Lu, Liang
AU  - Lu L
AD  - Department of Pharmacology, School of Pharmacy , Fourth Military Medical 
      University , Xi'an 710032 , China.
FAU - Zhang, Kun
AU  - Zhang K
AD  - Department of Pharmacology, School of Pharmacy , Fourth Military Medical 
      University , Xi'an 710032 , China.
FAU - Wang, Ya-Tao
AU  - Wang YT
AD  - Department of Pharmacology, School of Pharmacy , Fourth Military Medical 
      University , Xi'an 710032 , China.
FAU - Liu, Shui-Bing
AU  - Liu SB
AUID- ORCID: 0000-0002-9325-3474
AD  - Department of Pharmacology, School of Pharmacy , Fourth Military Medical 
      University , Xi'an 710032 , China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191004
PL  - United States
TA  - ACS Chem Neurosci
JT  - ACS chemical neuroscience
JID - 101525337
RN  - 0 
      (1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone)
RN  - 0 (4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta(c)quinoline)
RN  - 0 (Benzodioxoles)
RN  - 0 (Cyclopentanes)
RN  - 0 (GPER1 protein, mouse)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Quinolines)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Autophagy/*drug effects
MH  - Benzodioxoles/pharmacology
MH  - Cell Survival/drug effects
MH  - Cerebral Cortex/drug effects/metabolism
MH  - Cyclopentanes/pharmacology
MH  - Glutamic Acid/*pharmacology
MH  - Mice
MH  - Neurons/*drug effects/metabolism
MH  - Neuroprotective Agents/*pharmacology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Quinolines/pharmacology
MH  - Receptors, Estrogen/antagonists & inhibitors/metabolism
MH  - Receptors, G-Protein-Coupled/*agonists/antagonists & inhibitors/metabolism
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - GPR30
OT  - autophagy
OT  - excitotoxicity
OT  - glutamate
OT  - mTOR
OT  - neuron
EDAT- 2019/09/24 06:00
MHDA- 2020/09/05 06:00
CRDT- 2019/09/24 06:00
PHST- 2019/09/24 06:00 [pubmed]
PHST- 2020/09/05 06:00 [medline]
PHST- 2019/09/24 06:00 [entrez]
AID - 10.1021/acschemneuro.9b00287 [doi]
PST - ppublish
SO  - ACS Chem Neurosci. 2019 Oct 16;10(10):4227-4236. doi: 
      10.1021/acschemneuro.9b00287. Epub 2019 Oct 4.