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Advanced glycation end products induce actin rearrangement and subsequent hyperpermeability of endothelial cells

Guo, Xiao-Hua ; Huang, Qiao-Bing ; Chen, Bo ; Wang, Shu-Yun ; Li, Qiang ; Zhu, Yan-Jun ; Hou, Fan-Fan ; Fu, Ning ; Brunk, Ulf T. and Zhao, Ming LU (2006) In APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 114(12). p.874-883
Abstract
This study aimed to determine the effects of advanced glycation end products (AGEs) on endothelial cytoskeleton morphology and permeability, and to detect the underlying signaling mechanisms involved in these responses. Cultured endothelial cells (ECs) were exposed to AGE-modified human serum albumin (AGE-HSA), and EC cytoskeletal changes were evaluated by observing fluorescence of F-actin following ligation with labeled antibodies. Endothelial permeability was detected by measuring the flux of TRITC-albumin across the EC monolayers. To explore the signaling pathways behind AGE-induced EC alteration, ECs were treated with either soluble anti-AGE receptor (RAGE) IgG, or the MAPK inhibitors PD98059 and SB203580 before AGE-HSA administration.... (More)
This study aimed to determine the effects of advanced glycation end products (AGEs) on endothelial cytoskeleton morphology and permeability, and to detect the underlying signaling mechanisms involved in these responses. Cultured endothelial cells (ECs) were exposed to AGE-modified human serum albumin (AGE-HSA), and EC cytoskeletal changes were evaluated by observing fluorescence of F-actin following ligation with labeled antibodies. Endothelial permeability was detected by measuring the flux of TRITC-albumin across the EC monolayers. To explore the signaling pathways behind AGE-induced EC alteration, ECs were treated with either soluble anti-AGE receptor (RAGE) IgG, or the MAPK inhibitors PD98059 and SB203580 before AGE-HSA administration. To further elucidate possible involvement of the ERK and p38 pathways in AGE-induced EC changes, adenovirus-carried recombinant constitutive dominant-negative forms of upstream ERK and p38 kinases, namely MEK1(A) and MKK6b(A), were pre-infected into ECs 24 h prior to AGE-HSA exposure. AGE-HSA induced actin cytoskeleton rearrangement, as well as EC hyperpermeability, in a dose and time-dependent manner. The effects were attenuated in cells pretreated with anti-RAGE IgG, PD98059 or SB203580, respectively. EC pre-infection with MEK1(A) and MKK6b(A) also alleviated the effect of AGEs. Furthermore, adenovirus-mediated administration of activated forms of either MEK1 or MKK6b alone induced rearrangement of F-actin and hyperpermeability. The results indicate that ERK and p38 MAPK play important roles in the mediation of AGE-induced EC barrier dysfunction associated with morphological changes of the F-actin. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
MAPK, cytoskeleton, actin, advanced glycation end products (AGEs), endothelial cells
in
APMIS : acta pathologica, microbiologica, et immunologica Scandinavica
volume
114
issue
12
pages
874 - 883
publisher
John Wiley & Sons
external identifiers
  • wos:000242902800007
  • scopus:33845697912
  • pmid:17207088
ISSN
1600-0463
DOI
10.1111/j.1600-0463.2006.apm_372.x
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medical Inflammation Research (013212019), Experimental Cardiovascular Research Unit (013242110)
id
71bc7eae-0bc8-4b4d-aabc-ac4ccaea712d (old id 682010)
date added to LUP
2016-04-01 11:46:40
date last changed
2020-01-15 02:25:44
@article{71bc7eae-0bc8-4b4d-aabc-ac4ccaea712d,
  abstract     = {This study aimed to determine the effects of advanced glycation end products (AGEs) on endothelial cytoskeleton morphology and permeability, and to detect the underlying signaling mechanisms involved in these responses. Cultured endothelial cells (ECs) were exposed to AGE-modified human serum albumin (AGE-HSA), and EC cytoskeletal changes were evaluated by observing fluorescence of F-actin following ligation with labeled antibodies. Endothelial permeability was detected by measuring the flux of TRITC-albumin across the EC monolayers. To explore the signaling pathways behind AGE-induced EC alteration, ECs were treated with either soluble anti-AGE receptor (RAGE) IgG, or the MAPK inhibitors PD98059 and SB203580 before AGE-HSA administration. To further elucidate possible involvement of the ERK and p38 pathways in AGE-induced EC changes, adenovirus-carried recombinant constitutive dominant-negative forms of upstream ERK and p38 kinases, namely MEK1(A) and MKK6b(A), were pre-infected into ECs 24 h prior to AGE-HSA exposure. AGE-HSA induced actin cytoskeleton rearrangement, as well as EC hyperpermeability, in a dose and time-dependent manner. The effects were attenuated in cells pretreated with anti-RAGE IgG, PD98059 or SB203580, respectively. EC pre-infection with MEK1(A) and MKK6b(A) also alleviated the effect of AGEs. Furthermore, adenovirus-mediated administration of activated forms of either MEK1 or MKK6b alone induced rearrangement of F-actin and hyperpermeability. The results indicate that ERK and p38 MAPK play important roles in the mediation of AGE-induced EC barrier dysfunction associated with morphological changes of the F-actin.},
  author       = {Guo, Xiao-Hua and Huang, Qiao-Bing and Chen, Bo and Wang, Shu-Yun and Li, Qiang and Zhu, Yan-Jun and Hou, Fan-Fan and Fu, Ning and Brunk, Ulf T. and Zhao, Ming},
  issn         = {1600-0463},
  language     = {eng},
  number       = {12},
  pages        = {874--883},
  publisher    = {John Wiley & Sons},
  series       = { APMIS : acta pathologica, microbiologica, et immunologica Scandinavica},
  title        = {Advanced glycation end products induce actin rearrangement and subsequent hyperpermeability of endothelial cells},
  url          = {http://dx.doi.org/10.1111/j.1600-0463.2006.apm_372.x},
  doi          = {10.1111/j.1600-0463.2006.apm_372.x},
  volume       = {114},
  year         = {2006},
}