PMID- 21924080
OWN - NLM
STAT- MEDLINE
DCOM- 20120702
LR  - 20110919
IS  - 0253-3758 (Print)
IS  - 0253-3758 (Linking)
VI  - 39
IP  - 6
DP  - 2011 Jun
TI  - [Tumor necrosis factor-alpha promote permeability of human umbilical vein endothelial 
      cells via activating RhoA-ERK1/2 pathway].
PG  - 531-7
AB  - OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is known to induce changes in 
      endothelial cell morphology and permeability. The aim of this study is to 
      determine the underlying signaling mechanisms involved in these responses. 
      METHODS: Cultured human umbilical vein endothelial cells (HUVECs) were exposed to 
      TNF-alpha, and HUVEC cytoskeletal changes were evaluated by observing fluorescence of 
      F-actin following ligation with labeled antibodies. Endothelial permeability was 
      detected by measuring the flux of horseradish peroxidase (HRP)-albumin across the 
      EC monolayers. To explore the signaling pathways behind TNF-alpha-induced changes in 
      HUVEC morphology and permeability, HUVECs were treated with either the Rho GTPase 
      inhibitor Y27632 or the mitogen-activated protein kinases (MAPK) inhibitors 
      PD98059 and SB203580 before TNF-alpha administration. To further elucidate possible 
      involvement of the RhoA and ERK pathways in TNF-alpha-induced HUVEC changes, 
      retrovirus-carried recombinant dominant-negative forms and 
      constitutive-activative forms of RhoA, namely T19NRhoA and Q63LRhoA, were 
      pre-infected into HUVECs prior to TNF-alpha exposure. RESULTS: TNF-alpha induced F-actin 
      cytoskeleton rearrangement and increased HUVEC permeability in a dose and 
      time-dependent manner. The maximal increase in the HRP-BSA flux (40 ng/ml) was 
      seen in cells exposed to TNF-alpha at 100 ng/ml after 2 h. Preconditioning of HUVEC 
      monolayer with Y27632 or PD98059 significantly reduced TNF-alpha induced permeability 
      increase (HRP concentration from 40 ng/ml decreased to 12.5 ng/ml, P < 0.05) and 
      F-actin cytoskeleton rearrangement, HUVEC pre-infection with activated forms of 
      Q63LRhoA increased HUVEC permeability and upregulated pERK compared to GFP 
      infection, while HUVEC pre-infection with inhibited forms of T19NRhoA attenuated 
      the effects of TNF-alpha on HUVEC permeability. CONCLUSION: These results indicate 
      that TNF-alpha-induced EC barrier dysfunction and morphological changes of the 
      F-actin via activating RhoA-ERK/MAPK signal pathway.
FAU - Yan, Cheng-Hui
AU  - Yan CH
AD  - Department of Cardiology, Shenyang General Hospital, Shenyang 110840, China.
FAU - Yu, Hai-Bo
AU  - Yu HB
FAU - Huang, Ming-Fang
AU  - Huang MF
FAU - Li, Jie
AU  - Li J
FAU - Zhang, Xiao-Lin
AU  - Zhang XL
FAU - Han, Ya-Ling
AU  - Han YL
LA  - chi
PT  - English Abstract
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Zhonghua Xin Xue Guan Bing Za Zhi
JT  - Zhonghua xin xue guan bing za zhi
JID - 7910682
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
SB  - IM
MH  - *Cell Membrane Permeability
MH  - Cells, Cultured
MH  - Cytoskeleton/*metabolism
MH  - Endothelial Cells/cytology/drug effects/metabolism
MH  - Endothelium, Vascular/cytology
MH  - Human Umbilical Vein Endothelial Cells/drug effects
MH  - Humans
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Signal Transduction
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - rhoA GTP-Binding Protein/*metabolism
EDAT- 2011/09/20 06:00
MHDA- 2012/07/03 06:00
CRDT- 2011/09/20 06:00
PHST- 2011/09/20 06:00 [entrez]
PHST- 2011/09/20 06:00 [pubmed]
PHST- 2012/07/03 06:00 [medline]
PST - ppublish
SO  - Zhonghua Xin Xue Guan Bing Za Zhi. 2011 Jun;39(6):531-7.