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http://purl.uniprot.org/citations/18559661http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18559661http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18559661http://www.w3.org/2000/01/rdf-schema#comment"

Objective

We examined the effect of the vasoactive agents carbon monoxide (CO) and nitric oxide (NO) : n the phosphorylation and intracellular redistribution of vasodilator-stimulated phosphoprotein (VASP), a critical actin motor protein required for cell migration that also controls vasodilation and platelet aggregation.

Research design and methods

We examined the effect of donor-released CO and NO in endothelial progenitor cells (EPCs) and platelets from nondiabetic and diabetic subjects and in human microvascular endothelial cells (HMECs) cultured under low (5.5 mmol/l) or high (25 mmol/l) glucose conditions. VASP phosphorylation was evaluated using phosphorylation site-specific antibodies.

Results

In control platelets, CO selectively promotes phosphorylation at VASP Ser-157, whereas NO promotes phosphorylation primarily at Ser-157 and also at Ser-239, with maximal responses at 1 min with both agents on Ser-157 and at 15 min on Ser-239 with NO treatment. In diabetic platelets, neither agent resulted in VASP phosphorylation. In nondiabetic EPCs, NO and CO increased phosphorylation at Ser-239 and Ser-157, respectively, but this response was markedly reduced in diabetic EPCs. In endothelial cells cultured under low glucose conditions, both CO and NO induced phosphorylation at Ser-157 and Ser-239; however, this response was completely lost when cells were cultured under high glucose conditions. In control EPCs and in HMECs exposed to low glucose, VASP was redistributed to filopodia-like structures following CO or NO exposure; however, redistribution was dramatically attenuated under high glucose conditions.

Conclusions

Vasoactive gases CO and NO promote cytoskeletal changes through site- and cell type-specific VASP phosphorylation, and in diabetes, blunted responses to these agents may lead to reduced vascular repair and tissue perfusion."xsd:string
http://purl.uniprot.org/citations/18559661http://purl.org/dc/terms/identifier"doi:10.2337/db08-0381"xsd:string
http://purl.uniprot.org/citations/18559661http://purl.org/dc/terms/identifier"doi:10.2337/db08-0381"xsd:string
http://purl.uniprot.org/citations/18559661http://purl.uniprot.org/core/author"Agarwal A."xsd:string
http://purl.uniprot.org/citations/18559661http://purl.uniprot.org/core/author"Agarwal A."xsd:string
http://purl.uniprot.org/citations/18559661http://purl.uniprot.org/core/author"Nakagawa T."xsd:string
http://purl.uniprot.org/citations/18559661http://purl.uniprot.org/core/author"Nakagawa T."xsd:string
http://purl.uniprot.org/citations/18559661http://purl.uniprot.org/core/author"Chang K.H."xsd:string
http://purl.uniprot.org/citations/18559661http://purl.uniprot.org/core/author"Chang K.H."xsd:string
http://purl.uniprot.org/citations/18559661http://purl.uniprot.org/core/author"Afzal A."xsd:string
http://purl.uniprot.org/citations/18559661http://purl.uniprot.org/core/author"Afzal A."xsd:string
http://purl.uniprot.org/citations/18559661http://purl.uniprot.org/core/author"Purich D.L."xsd:string
http://purl.uniprot.org/citations/18559661http://purl.uniprot.org/core/author"Purich D.L."xsd:string
http://purl.uniprot.org/citations/18559661http://purl.uniprot.org/core/author"Busik J.V."xsd:string
http://purl.uniprot.org/citations/18559661http://purl.uniprot.org/core/author"Busik J.V."xsd:string
http://purl.uniprot.org/citations/18559661http://purl.uniprot.org/core/author"Grant M.B."xsd:string
http://purl.uniprot.org/citations/18559661http://purl.uniprot.org/core/author"Grant M.B."xsd:string
http://purl.uniprot.org/citations/18559661http://purl.uniprot.org/core/author"Li Calzi S."xsd:string
http://purl.uniprot.org/citations/18559661http://purl.uniprot.org/core/author"Li Calzi S."xsd:string
http://purl.uniprot.org/citations/18559661http://purl.uniprot.org/core/author"Segal M.S."xsd:string
http://purl.uniprot.org/citations/18559661http://purl.uniprot.org/core/author"Segal M.S."xsd:string
http://purl.uniprot.org/citations/18559661http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/18559661http://purl.uniprot.org/core/date"2008"xsd:gYear
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