PMID- 35257817
OWN - NLM
STAT- MEDLINE
DCOM- 20220502
LR  - 20220502
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 470
DP  - 2022 Mar 30
TI  - N-methyl-D-aspartic acid increases tight junction protein destruction in brain 
      endothelial cell via caveolin-1-associated ERK1/2 signaling.
PG  - 153139
LID - S0300-483X(22)00051-8 [pii]
LID - 10.1016/j.tox.2022.153139 [doi]
AB  - N-methyl-D-aspartic acid (NMDA), a glutamate analog, can activate 
      N-Methyl-D-Aspartate receptor (NMDAR) to induce vascular endothelial cell injury 
      but the mechanisms are not fully understood. The present study intended to 
      evaluate the role of caveolin-1 (Cav-1) in NMDA-induced dysfunction of human 
      brain microvascular endothelial cells (HBEC-5i), and verify that endothelial 
      NMDAR activation mediates the disruption of tight junction barrier integrity via 
      extracellular signal-regulated kinase (ERK)1/2 pathway. The expression of NMDAR 
      NR1 were confirmed firstly in HBEC-5i and compared with that in mouse brain by 
      Western blot. To study the role of Cav-1 in NMDA mediated reduction of tight 
      junction protein zonula occludens- (ZO) 1 expression, HBEC-5i were transduced 
      with Cav-1 shRNA or Control shRNA, and the Cav-1 knockdown rate tested with 
      qRT-PCR and Western blot is 99.98% or 87.5%, respectively. NMDA exposure 
      decreased mRNA and protein levels of tight junction protein ZO-1 and suppressed 
      transendothelial electrical resistance (TEER) values in HBEC-5i but blocked by 
      NMDAR antagonist MK801. In addition, NMDA induced Cav-1 and ERK1/2 sequential 
      phosphorylation，but these effects were attenuated by silencing the Cav-1 gene 
      with shRNA and ERK1/2 inhibitor U0126, respectively. These results show that the 
      functional presence of NMDAR NR1 in HBEC-5i. Endothelial NMDAR NR1 activation 
      regulate the maintenance of HBEC-5i-constructed tight junction barrier integrity 
      via the caveolin-1-associated ERK1/2 signaling pathway.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Mao, Fengping
AU  - Mao F
AD  - Department of Neurology, First Affiliated Hospital, Guangxi Medical University, 
      Nanning 530021, PR China.
FAU - Huang, Fang
AU  - Huang F
AD  - Department of Neurology, First Affiliated Hospital, Guangxi Medical University, 
      Nanning 530021, PR China.
FAU - Nong, Weidong
AU  - Nong W
AD  - Department of Neurology, First Affiliated Hospital, Guangxi Medical University, 
      Nanning 530021, PR China.
FAU - Lao, Dayuan
AU  - Lao D
AD  - Department of Neurology, First Affiliated Hospital, Guangxi Medical University, 
      Nanning 530021, PR China.
FAU - Gong, Zhuowei
AU  - Gong Z
AD  - Department of Neurology, First Affiliated Hospital, Guangxi Medical University, 
      Nanning 530021, PR China.
FAU - Huang, Wen
AU  - Huang W
AD  - Department of Neurology, First Affiliated Hospital, Guangxi Medical University, 
      Nanning 530021, PR China. Electronic address: hwen1229@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220304
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Caveolin 1)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Tight Junction Proteins)
RN  - 0 (Zonula Occludens-1 Protein)
RN  - 6384-92-5 (N-Methylaspartate)
SB  - IM
MH  - Animals
MH  - Brain/metabolism
MH  - *Caveolin 1/genetics/metabolism
MH  - Endothelial Cells
MH  - Humans
MH  - MAP Kinase Signaling System
MH  - Mice
MH  - *N-Methylaspartate/toxicity
MH  - RNA, Small Interfering/pharmacology
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Signal Transduction
MH  - Tight Junction Proteins
MH  - Tight Junctions/metabolism
MH  - Zonula Occludens-1 Protein/genetics/metabolism
OTO - NOTNLM
OT  - Caveolin-1
OT  - ERK1/2 signaling
OT  - Human cerebrovascular endothelial cells
OT  - N-methyl-D-aspartic acid
OT  - ZO-1
EDAT- 2022/03/09 06:00
MHDA- 2022/05/03 06:00
CRDT- 2022/03/08 08:44
PHST- 2021/12/06 00:00 [received]
PHST- 2022/02/21 00:00 [revised]
PHST- 2022/02/28 00:00 [accepted]
PHST- 2022/03/09 06:00 [pubmed]
PHST- 2022/05/03 06:00 [medline]
PHST- 2022/03/08 08:44 [entrez]
AID - S0300-483X(22)00051-8 [pii]
AID - 10.1016/j.tox.2022.153139 [doi]
PST - ppublish
SO  - Toxicology. 2022 Mar 30;470:153139. doi: 10.1016/j.tox.2022.153139. Epub 2022 Mar 
      4.