RGD Reference Report - Diabetes regulates small molecular weight G-protein, H-Ras, in the microvasculature of the retina: implication in the development of retinopathy. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Diabetes regulates small molecular weight G-protein, H-Ras, in the microvasculature of the retina: implication in the development of retinopathy.

Authors: Kanwar, M  Kowluru, RA 
Citation: Kanwar M and Kowluru RA, Microvasc Res. 2008 Nov;76(3):189-93. Epub 2008 Apr 25.
RGD ID: 2314841
Pubmed: PMID:18514235   (View Abstract at PubMed)
PMCID: PMC2695828   (View Article at PubMed Central)
DOI: DOI:10.1016/j.mvr.2008.04.002   (Journal Full-text)

Retinopathy, a largely microvascular complication, affects over 80% of patients with diabetes for 20 years. The purpose of this study is to investigate the effect of diabetes on the activation of H-Ras, a small molecular weight G-protein that regulates cell fate, in the retinal microvessels. Microvessels were prepared from freshly isolated retina from streptozotocin diabetic rats or 30% galactose-fed rats by hypotonic lysis method. Ras activation was quantified by Raf-1 binding assay, and the activation of the signaling proteins, Raf-1 and mitogen activated protein (MAP) kinase, by quantifying their gene transcripts (RTPCR) and/or by protein expression (western blot). Two months of diabetes or experimental galactosemia activated H-Ras (Raf-binding assay) in the retinal microvessels by over 40% and 70% respectively compared to the values obtained from normal rat retinal microvessels. In the same diabetic rats the gene transcripts of H-Ras and its effector protein Raf-1 were elevated by 30% and 135% respectively with their protein expressions elevated by about 25% each, and this was paralleled by similar increases in the protein expressions of H-Ras and Raf-1 in experimentally galactosemic rats. Diabetes increased the gene expression of Ras-Raf-1 downstream signaling protein MAP kinase by over 50%, and that of nuclear transcriptional factor by 25-30%. This activation of H-Ras in retinal microvessels implies that its signaling pathway, in part, could be contributing to the microvascular pathology characteristic of diabetic retinopathy. Comparable activation of H-Ras and its signaling cascade in the retinal microvessels from experimentally galactosemic rats suggests that H-Ras activation is not due to insulin deficiency. Regulation of Ras function could provide important target in the complex approach to inhibit the pathogenesis of diabetic retinopathy.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Experimental Diabetes Mellitus  ISOHras (Rattus norvegicus)2314841; 2314841mRNA and protein:increased expression:retina blood vesselRGD 
Experimental Diabetes Mellitus  IEP 2314841mRNA and protein:increased expression:retina blood vesselRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding  IPIRaf1 (Rattus norvegicus)2314841 RGD 
protein binding  IPIHras (Rattus norvegicus)2314841 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hras  (HRas proto-oncogene, GTPase)
Raf1  (Raf-1 proto-oncogene, serine/threonine kinase)

Genes (Mus musculus)
Hras  (Harvey rat sarcoma virus oncogene)

Genes (Homo sapiens)
HRAS  (HRas proto-oncogene, GTPase)


Additional Information