RGD Reference Report - High-glucose-induced structural changes in the heparan sulfate proteoglycan, perlecan, of cultured human aortic endothelial cells. - Rat Genome Database

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High-glucose-induced structural changes in the heparan sulfate proteoglycan, perlecan, of cultured human aortic endothelial cells.

Authors: Vogl-Willis, CA  Edwards, IJ 
Citation: Vogl-Willis CA and Edwards IJ, Biochim Biophys Acta. 2004 Apr 7;1672(1):36-45.
RGD ID: 1624255
Pubmed: PMID:15056491   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bbagen.2004.02.005   (Journal Full-text)

Hyperglycemia is an independent risk factor for diabetes-associated cardiovascular disease. One potential mechanism involves hyperglycemia-induced changes in arterial wall extracellular matrix components leading to increased atherosclerosis susceptibility. A decrease in heparan sulfate (HS) glycosaminoglycans (GAG) has been reported in diabetic arteries. The present studies examined the effects of high glucose on in vitro production of proteoglycans (PG) by aortic endothelial cells. Exposure of cells to high glucose (30 vs. 5 mM glucose) resulted in decreased [(35)S] sodium sulfate incorporation specifically into secreted HSPG. Differences were not due to hyperosmolar effects and no changes were observed in CS/DSPG. Enzymatic procedures, immunoprecipitation and Western analyses demonstrated that high glucose induced changes specifically in the HSPG, perlecan. In double-label experiments, lower sulfate incorporation in high-glucose-treated cells was accompanied by lower [(3)H] glucosamine incorporation into GAG but not lower [(3)H] serine incorporation into PG core proteins. Size exclusion chromatography demonstrated that GAG size was unchanged and GAG sulfation was not reduced. These results indicate that the level of regulation of perlecan by high glucose is posttranslational, involving a modification in molecular structure, possibly a decrease in the number of HS GAG chains on the core protein.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HSPG2Humanhyperglycemia  IEP protein:decreased expression:endothelial cellRGD 
Hspg2Rathyperglycemia  ISOHSPG2 (Homo sapiens)protein:decreased expression:endothelial cellRGD 
Hspg2Mousehyperglycemia  ISOHSPG2 (Homo sapiens)protein:decreased expression:endothelial cellRGD 

Objects Annotated

Genes (Rattus norvegicus)
Hspg2  (heparan sulfate proteoglycan 2)

Genes (Mus musculus)
Hspg2  (perlecan (heparan sulfate proteoglycan 2))

Genes (Homo sapiens)
HSPG2  (heparan sulfate proteoglycan 2)


Additional Information