Linked Life Data

19395553

Source:http://linkedlifedata.com/resource/pubmed/id/19395553

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-6-30
pubmed:abstractText
Advanced glycation end products (AGEs) accumulated in different pathological conditions have the potent capacity to alter cellular properties that include endothelial structural and functional regulations. The disruption of endothelial barrier integrity may contribute to AGE-induced microangiopathy and macrovasculopathy. Previous studies have shown that AGEs induced the rearrangement of actin and subsequent hyperpermeability in endothelial cells (ECs). However, the mechanisms involved in this AGE-evoked EC malfunction are not well understood. This study directly evaluated the involvement of moesin phosphorylation in AGE-induced alterations and the effects of the RhoA and p38 MAPK pathways on this process. Using immortalized human dermal microvascular ECs (HMVECs), we first confirmed that the ezrin/radixin/moesin (ERM) protein moesin is required in AGE-induced F-actin rearrangement and hyperpermeability responses in ECs by knockdown of moesin protein expression with small interfering RNA. We then detected AGE-induced moesin phosphorylation by Western blot analysis. The mechanisms involved in moesin phosphorylation were analyzed by blocking AGE receptor binding and inhibiting Rho and MAPK pathways. AGE-treated HMVECs exhibited time- and dose-dependent increases in the Thr(558) phosphorylation of moesin. The increased moesin phosphorylation was attenuated by preadministrations of AGE receptor antibody, Rho kinase (ROCK), or p38 inhibitor. Suppression of p38 activation via the expression of dominant negative mutants with Ad.MKK6b or Ad.p38alpha also decreased moesin phosphorylation. The activation of the p38 pathway by transfection of HMVECs with an adenoviral construct of dominant active MKK6b resulted in moesin phosphorylation. These results suggest a critical role of moesin phosphorylation in AGE-induced EC functional and morphological regulations. Activation of the ROCK and p38 pathways is required in moesin phosphorylation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1522-1539
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
297
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H238-46
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:19395553-Adenoviridae, pubmed-meshheading:19395553-Animals, pubmed-meshheading:19395553-Blotting, Western, pubmed-meshheading:19395553-Capillary Permeability, pubmed-meshheading:19395553-Cells, Cultured, pubmed-meshheading:19395553-Computer Simulation, pubmed-meshheading:19395553-Cytoskeleton, pubmed-meshheading:19395553-Endothelium, Vascular, pubmed-meshheading:19395553-Fluorescent Dyes, pubmed-meshheading:19395553-Genetic Vectors, pubmed-meshheading:19395553-Glycosylation End Products, Advanced, pubmed-meshheading:19395553-Humans, pubmed-meshheading:19395553-Mice, pubmed-meshheading:19395553-Microfilament Proteins, pubmed-meshheading:19395553-Phosphorylation, pubmed-meshheading:19395553-RNA, Small Interfering, pubmed-meshheading:19395553-Signal Transduction, pubmed-meshheading:19395553-p38 Mitogen-Activated Protein Kinases, pubmed-meshheading:19395553-rho-Associated Kinases
pubmed:year
2009
pubmed:articleTitle
ERM protein moesin is phosphorylated by advanced glycation end products and modulates endothelial permeability.
pubmed:affiliation
Department of Pathophysiology, Southern Medical University, Guangzhou, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't