Linked Life Data

16840537

Source:http://linkedlifedata.com/resource/pubmed/id/16840537

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2006-10-26
pubmed:abstractText
Angiogenesis impairment in hyperglycemic patients represents a leading cause of severe vascular complications of both type-1 and -2 diabetes mellitus (DM). Angiogenesis dysfunction in DM is related to glycemic control; however, molecular mechanisms involved are still unclear. Fibroblast growth factor-2 (FGF-2) is a potent angiogenic factor and, according to previous evidence, may represent a key target of molecular modifications triggered by high-sugar exposure. Therefore, the purpose of this study was to investigate whether short incubation with hyperglycemic levels of glucose affected FGF-2 and whether glucose-modified FGF-2 was detectable in vivo. Biochemical analyses carried out with SDS-PAGE, fluorescence emission, mass-spectrometry, immunoblot, and competitive ELISA experiments demonstrated that human FGF-2 undergoes a rapid and specific glycation upon 12.5-50 mm glucose exposure. In addition, FGF-2 exposed for 30 min to 12.5 mm glucose lost mitogenic and chemotactic activity in a time- and dose-dependent manner. Under similar conditions, binding affinity to FGF receptor 1 was dramatically reduced by 20-fold, as well as FGF receptor 1 and ERK-1/2 phosphorylation, and FGF-2 lost about 45% of angiogenic activity in two different in vivo angiogenic (Matrigel and chorioallantoic-membrane) assays. Such glucose-induced modification was specific, because other angiogenic growth factors, namely platelet-derived growth factor BB and placental-derived growth factor were not significantly or markedly less modified. Finally, for the first time, glycated-FGF-2 was detected in vivo, in tissues from hyperglycemic nonobese diabetic mice, in significantly higher amounts than in normoglycemic mice. In conclusion, hyperglycemic levels of glucose may strongly affect FGF-2 structure and impair its angiogenic features, and endogenous glycated-FGF-2 is present in diabetic mice, indicating a novel pathogenetic mechanism underlying angiogenesis defects in DM.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0888-8809
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2806-18
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16840537-Animals, pubmed-meshheading:16840537-Binding, Competitive, pubmed-meshheading:16840537-Blood Glucose, pubmed-meshheading:16840537-Cattle, pubmed-meshheading:16840537-Cells, Cultured, pubmed-meshheading:16840537-Chemokines, pubmed-meshheading:16840537-Diabetes Mellitus, Experimental, pubmed-meshheading:16840537-Dose-Response Relationship, Drug, pubmed-meshheading:16840537-Female, pubmed-meshheading:16840537-Fibroblast Growth Factor 2, pubmed-meshheading:16840537-Glucose, pubmed-meshheading:16840537-Glycosylation, pubmed-meshheading:16840537-Glycosylation End Products, Advanced, pubmed-meshheading:16840537-Growth Substances, pubmed-meshheading:16840537-Humans, pubmed-meshheading:16840537-Hyperglycemia, pubmed-meshheading:16840537-Mice, pubmed-meshheading:16840537-Mice, Inbred NOD, pubmed-meshheading:16840537-Neovascularization, Physiologic, pubmed-meshheading:16840537-Receptor, Fibroblast Growth Factor, Type 1
pubmed:year
2006
pubmed:articleTitle
Glycated fibroblast growth factor-2 is quickly produced in vitro upon low-millimolar glucose treatment and detected in vivo in diabetic mice.
pubmed:affiliation
Dipartimento di Ematologia, Oncologia e Medicina Molecolare, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Roma, Italy. facchian@iss.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't