PMID- 32413421
OWN - NLM
STAT- MEDLINE
DCOM- 20200827
LR  - 20200827
IS  - 1879-3185 (Electronic)
IS  - 0300-483X (Linking)
VI  - 440
DP  - 2020 Jul
TI  - Paracellular permeability changes induced by multi-walled carbon nanotubes in 
      brain endothelial cells and associated roles of hemichannels.
PG  - 152491
LID - S0300-483X(20)30130-X [pii]
LID - 10.1016/j.tox.2020.152491 [doi]
AB  - Multi-walled carbon nanotubes (MWCNTs) have promising applications in neurology 
      depending on their unique physicochemical properties. However, there is limited 
      understanding of their impacts on brain microvascular endothelial cells, the 
      cells lining the vessels and maintaining the low and selective permeability of 
      the blood-brain barrier. In this study, we examined the influence of pristine 
      MWCNT (p-MWCNT) and carboxylated MWCNT (c-MWCNT) on permeability and tight 
      junction tightness of murine brain microvascular endothelial cells, and 
      investigated the potential mechanisms in the sight of hemichannel activity. 
      Treatment with p-MWCNT for 24 h at subtoxic concentration (20 mug/mL) decreased 
      the protein expression of occludin, disrupted zonula occludens-1 continuity, and 
      elevated monolayer permeability as quantified by transendothelial electrical 
      resistance and paracellular flux of 4000 Da fluorescein isothiocyanate-dextran 
      conjugates. Moreover, p-MWCNT exposure also increased hemichannel activity with 
      upregulated protein expression and altered subcellular localization of connexin 
      (Cx)43 and pannexin (Panx)1. p-MWCNT-induced elevation in endothelial 
      permeability could be prevented by hemichannel inhibitor carbenoxolone and 
      peptide blocker of Cx43 and Panx1, indicating the crucial role of activated Cx43 
      and Panx1 hemichannels. Furthermore, Cx43 and Panx1 hemichannel-mediated ATP 
      release might be involved in p-MWCNT-induced rise in endothelial permeability. In 
      contrast, the above effects caused by p-MWCNT were not observed in cells treated 
      with c-MWCNT, the functionalized form with more stable dispersion and a lower 
      tendency to aggregate. Our study contributes further understanding of the impact 
      of MWCNTs on brain endothelial tightness and permeability, which may have 
      important implications for the safety application of MWCNTs in nanomedicine.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Yang, Di
AU  - Yang D
AD  - Department of Occupational and Environmental Health Sciences, School of Public 
      Health, Peking University, No. 38 Xueyuan Road, Beijing 100191, China.
FAU - Shen, Jie
AU  - Shen J
AD  - Department of Occupational and Environmental Health Sciences, School of Public 
      Health, Peking University, No. 38 Xueyuan Road, Beijing 100191, China.
FAU - Fan, Jingpu
AU  - Fan J
AD  - Department of Occupational and Environmental Health Sciences, School of Public 
      Health, Peking University, No. 38 Xueyuan Road, Beijing 100191, China.
FAU - Chen, Yiyong
AU  - Chen Y
AD  - Department of Occupational and Environmental Health Sciences, School of Public 
      Health, Peking University, No. 38 Xueyuan Road, Beijing 100191, China.
FAU - Guo, Xinbiao
AU  - Guo X
AD  - Department of Occupational and Environmental Health Sciences, School of Public 
      Health, Peking University, No. 38 Xueyuan Road, Beijing 100191, China. Electronic 
      address: guoxb@bjmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200513
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Connexin 43)
RN  - 0 (Connexins)
RN  - 0 (Nanotubes, Carbon)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Occludin)
RN  - 0 (Ocln protein, mouse)
RN  - 0 (Panx1 protein, mouse)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Blood-Brain Barrier/drug effects
MH  - Capillaries/cytology/drug effects/metabolism
MH  - Cell Line
MH  - Cell Membrane Permeability/drug effects
MH  - Cell Survival
MH  - Connexin 43/antagonists & inhibitors
MH  - Connexins/antagonists & inhibitors
MH  - Electric Impedance
MH  - Endothelial Cells/*drug effects
MH  - Mice
MH  - *Nanotubes, Carbon
MH  - Nerve Tissue Proteins/antagonists & inhibitors
MH  - Occludin/biosynthesis
MH  - Tight Junctions/drug effects
OTO - NOTNLM
OT  - Brain microvascular endothelial cell
OT  - Connexin 43
OT  - Hemichannel
OT  - Multi-walled carbon nanotubes
OT  - Pannexin1
OT  - Paracellular permeability
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/05/16 06:00
MHDA- 2020/08/28 06:00
CRDT- 2020/05/16 06:00
PHST- 2020/02/26 00:00 [received]
PHST- 2020/04/16 00:00 [revised]
PHST- 2020/05/04 00:00 [accepted]
PHST- 2020/05/16 06:00 [pubmed]
PHST- 2020/08/28 06:00 [medline]
PHST- 2020/05/16 06:00 [entrez]
AID - S0300-483X(20)30130-X [pii]
AID - 10.1016/j.tox.2020.152491 [doi]
PST - ppublish
SO  - Toxicology. 2020 Jul;440:152491. doi: 10.1016/j.tox.2020.152491. Epub 2020 May 
      13.