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http://purl.uniprot.org/citations/22251897http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22251897http://www.w3.org/2000/01/rdf-schema#comment"

Background

The role of advanced glycation end products (AGEs) in the development of diabetes, especially diabetic complications, has been emphasized in many reports. Accumulation of AGEs in the vasculature triggers a series of morphological and functional changes in endothelial cells (ECs) and induces an increase of endothelial permeability. This study was to investigate the involvement of RhoA/ROCK-dependent moesin phosphorylation in endothelial abnormalities induced by AGEs.

Methods

Using human dermal microvascular endothelial cells (HMVECs), the effects of human serum albumin modified-AGEs (AGE-HSA) on the endothelium were assessed by measuring monolayer permeability and staining of F-actin in HMVECs. Activations of RhoA and ROCK were determined by a luminescence-based assay and immunoblotting. Transfection of recombinant adenovirus that was dominant negative for RhoA (RhoA N19) was done to down-regulate RhoA expression, while adenovirus with constitutively activated RhoA (RhoA L63) was transfected to cause overexpression of RhoA in HMVECs. H-1152 was employed to specifically block activation of ROCK. Co-immunoprecipitation was used to further confirm the interaction of ROCK and its downstream target moesin. To identify AGE/ROCK-induced phosphorylation site in moesin, two mutants pcDNA3/HA-moesinT(558A) and pcDNA3/HA-moesinT(558D) were applied in endothelial cells.

Results

The results showed that AGE-HSA increased the permeability of HMVEC monolayer and triggered the formation of F-actin-positive stress fibers. AGE-HSA enhanced RhoA activity as well as phosphorylation of ROCK in a time- and dose-dependent manner. Down-regulation of RhoA expression with RhoA N19 transfection abolished these AGE-induced changes, while transfection of RhoA L63 reproduced the AGE-evoked changes. H-1152 attenuated the AGE-induced alteration in monolayer permeability and cytoskeleton. The results also confirmed the AGE-induced direct interaction of ROCK and moesin. Thr558 was further identified as the phosphorylating site of moesin in AGE-evoked endothelial responses.

Conclusion

These results confirm the involvement of RhoA/ROCK pathway and subsequent moesin Thr558 phosphorylation in AGE-mediated endothelial dysfunction."xsd:string
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http://purl.uniprot.org/citations/22251897http://purl.uniprot.org/core/author"Chen B."xsd:string
http://purl.uniprot.org/citations/22251897http://purl.uniprot.org/core/author"Guo X."xsd:string
http://purl.uniprot.org/citations/22251897http://purl.uniprot.org/core/author"Huang X."xsd:string
http://purl.uniprot.org/citations/22251897http://purl.uniprot.org/core/author"Huang Q."xsd:string
http://purl.uniprot.org/citations/22251897http://purl.uniprot.org/core/author"Liu H."xsd:string
http://purl.uniprot.org/citations/22251897http://purl.uniprot.org/core/author"Li Q."xsd:string
http://purl.uniprot.org/citations/22251897http://purl.uniprot.org/core/author"Wang J."xsd:string
http://purl.uniprot.org/citations/22251897http://purl.uniprot.org/core/author"Wang L."xsd:string
http://purl.uniprot.org/citations/22251897http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22251897http://purl.uniprot.org/core/name"Cardiovasc Diabetol"xsd:string
http://purl.uniprot.org/citations/22251897http://purl.uniprot.org/core/pages"7"xsd:string
http://purl.uniprot.org/citations/22251897http://purl.uniprot.org/core/title"RhoA/ROCK-dependent moesin phosphorylation regulates AGE-induced endothelial cellular response."xsd:string
http://purl.uniprot.org/citations/22251897http://purl.uniprot.org/core/volume"11"xsd:string
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