PMID- 27552214
OWN - NLM
STAT- MEDLINE
DCOM- 20171121
LR  - 20220408
IS  - 2213-2317 (Electronic)
IS  - 2213-2317 (Linking)
VI  - 9
DP  - 2016 Oct
TI  - Hydrogen sulfide metabolism regulates endothelial solute barrier function.
PG  - 157-166
LID - S2213-2317(16)30081-7 [pii]
LID - 10.1016/j.redox.2016.08.004 [doi]
AB  - Hydrogen sulfide (H(2)S) is an important gaseous signaling molecule in the 
      cardiovascular system. In addition to free H(2)S, H(2)S can be oxidized to 
      polysulfide which can be biologically active. Since the impact of H(2)S on 
      endothelial solute barrier function is not known, we sought to determine whether 
      H(2)S and its various metabolites affect endothelial permeability. In vitro 
      permeability was evaluated using albumin flux and transendothelial electrical 
      resistance. Different H(2)S donors were used to examine the effects of exogenous 
      H(2)S. To evaluate the role of endogenous H(2)S, mouse aortic endothelial cells 
      (MAECs) were isolated from wild type mice and mice lacking cystathionine gamma-lyase 
      (CSE), a predominant source of H(2)S in endothelial cells. In vivo permeability 
      was evaluated using the Miles assay. We observed that polysulfide donors induced 
      rapid albumin flux across endothelium. Comparatively, free sulfide donors 
      increased permeability only with higher concentrations and at later time points. 
      Increased solute permeability was associated with disruption of endothelial 
      junction proteins claudin 5 and VE-cadherin, along with enhanced actin stress 
      fiber formation. Importantly, sulfide donors that increase permeability elicited 
      a preferential increase in polysulfide levels within endothelium. Similarly, CSE 
      deficient MAECs showed enhanced solute barrier function along with reduced 
      endogenous bound sulfane sulfur. CSE siRNA knockdown also enhanced endothelial 
      junction structures with increased claudin 5 protein expression. In vivo, CSE 
      genetic deficiency significantly blunted VEGF induced hyperpermeability revealing 
      an important role of the enzyme for barrier function. In summary, endothelial 
      solute permeability is critically regulated via exogenous and endogenous sulfide 
      bioavailability with a prominent role of polysulfides.
CI  - Copyright (c) 2016 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Yuan, Shuai
AU  - Yuan S
AD  - Department of Cellular Biology and Anatomy, Louisiana State University Health 
      Sciences Center, Shreveport, LA 71103, USA.
FAU - Pardue, Sibile
AU  - Pardue S
AD  - Department of Pathology, Louisiana State University Health Sciences Center, 
      Shreveport, LA 71103, USA.
FAU - Shen, Xinggui
AU  - Shen X
AD  - Department of Pathology, Louisiana State University Health Sciences Center, 
      Shreveport, LA 71103, USA.
FAU - Alexander, J Steven
AU  - Alexander JS
AD  - Department of Molecular and Cellular Physiology, Louisiana State University 
      Health Sciences Center, Shreveport, LA 71103, USA.
FAU - Orr, A Wayne
AU  - Orr AW
AD  - Department of Cellular Biology and Anatomy, Louisiana State University Health 
      Sciences Center, Shreveport, LA 71103, USA; Department of Pathology, Louisiana 
      State University Health Sciences Center, Shreveport, LA 71103, USA.
FAU - Kevil, Christopher G
AU  - Kevil CG
AD  - Department of Cellular Biology and Anatomy, Louisiana State University Health 
      Sciences Center, Shreveport, LA 71103, USA; Department of Pathology, Louisiana 
      State University Health Sciences Center, Shreveport, LA 71103, USA; Department of 
      Molecular and Cellular Physiology, Louisiana State University Health Sciences 
      Center, Shreveport, LA 71103, USA; Center for Cardiovascular Diseases and 
      Sciences, Louisiana State University Health Sciences Center, Shreveport, LA 
      71103, USA. Electronic address: CKevil@lsuhsc.edu.
LA  - eng
GR  - R01 HL113303/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160811
PL  - Netherlands
TA  - Redox Biol
JT  - Redox biology
JID - 101605639
RN  - 0 (Actins)
RN  - 0 (Sulfides)
RN  - 9080-49-3 (polysulfide)
RN  - YY9FVM7NSN (Hydrogen Sulfide)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - Capillary Permeability/drug effects
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Endothelial Cells/drug effects/metabolism
MH  - Endothelium/drug effects/*metabolism
MH  - Humans
MH  - Hydrogen Sulfide/*metabolism/pharmacology
MH  - Intercellular Junctions/drug effects/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Oxidation-Reduction
MH  - Sulfides/metabolism
PMC - PMC4993857
OTO - NOTNLM
OT  - Cystathionine gamma-lyase
OT  - Endothelial permeability
OT  - Hydrogen sulfide
OT  - Polysulfide
EDAT- 2016/10/21 06:00
MHDA- 2017/11/29 06:00
PMCR- 2016/08/11
CRDT- 2016/08/24 06:00
PHST- 2016/07/22 00:00 [received]
PHST- 2016/08/03 00:00 [revised]
PHST- 2016/08/10 00:00 [accepted]
PHST- 2016/10/21 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2016/08/24 06:00 [entrez]
PHST- 2016/08/11 00:00 [pmc-release]
AID - S2213-2317(16)30081-7 [pii]
AID - 10.1016/j.redox.2016.08.004 [doi]
PST - ppublish
SO  - Redox Biol. 2016 Oct;9:157-166. doi: 10.1016/j.redox.2016.08.004. Epub 2016 Aug 
      11.