RGD Reference Report - Impaired function and expression of P-glycoprotein in blood-brain barrier of streptozotocin-induced diabetic rats. - Rat Genome Database

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Impaired function and expression of P-glycoprotein in blood-brain barrier of streptozotocin-induced diabetic rats.

Authors: Liu, H  Xu, X  Yang, Z  Deng, Y  Liu, X  Xie, L 
Citation: Liu H, etal., Brain Res. 2006 Dec 6;1123(1):245-52. Epub 2006 Oct 30.
RGD ID: 1598559
Pubmed: PMID:17074306   (View Abstract at PubMed)
DOI: DOI:10.1016/j.brainres.2006.09.061   (Journal Full-text)

The aim was to investigate the effect of diabetes mellitus (DM) on P-glycoprotein (P-GP) function and expression in rat blood-brain barrier (BBB). P-GP function in BBB was assessed by measuring the brain-to-plasma concentration ratios (Kp values) of rhodamine 123 (Rho123) and vincristine (VCR), two well-known P-GP substrates, in control rats and 5-week streptozotocin (STZ)-induced diabetic rats. Evans blue (EB) dye was used as a BBB integrity indicator for examining the extravasation from the blood into the brain. P-GP expression in the brain cortex was evaluated with Western blot. The uptakes of Rho123 and VCR by cultured rat brain microvessel endothelial cells (rBMECs) incubated in diabetic and control rat serum for 72 h were also used to examine P-GP function, respectively. It was found that the Kp value of Rho123 (0.022+/-0.005 vs. 0.016+/-0.002 ml/g brain, p=0.033) and VCR (0.072+/-0.028 vs. 0.023+/-0.006 ml/g brain, p=0.006) in diabetic rats was significantly higher than that in control rats. The uptakes of Rho123 and VCR by cultured rBMECs incubated in the diabetic rat serum were higher than that in the control rat serum, respectively. No significant difference of the EB concentration in the brain cortex was found between the diabetic rats and control rats. Electron microscope examination of the brain cortex did not show a clear damage to the endothelial cells of microvessel in diabetic rats. In addition, the protein level of P-GP in the brains of the diabetic rats examined was significantly lower than that of control rats. These results suggested that the function and expression of P-GP might be impaired in the BBB of STZ-induced diabetic rats.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ABCB1HumanExperimental Diabetes Mellitus  ISOAbcb1a (Rattus norvegicus)protein: decreased expressionRGD 
Abcb1aRatExperimental Diabetes Mellitus  IAGP protein: decreased expressionRGD 
Abcb1aMouseExperimental Diabetes Mellitus  ISOAbcb1a (Rattus norvegicus)protein: decreased expressionRGD 
Abcb1bRatExperimental Diabetes Mellitus  IDA  RGD 
Abcb1bMouseExperimental Diabetes Mellitus  ISOAbcb1b (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcb1a  (ATP binding cassette subfamily B member 1A)
Abcb1b  (ATP-binding cassette, sub-family B member 1B)

Genes (Mus musculus)
Abcb1a  (ATP-binding cassette, sub-family B member 1A)
Abcb1b  (ATP-binding cassette, sub-family B member 1B)

Genes (Homo sapiens)
ABCB1  (ATP binding cassette subfamily B member 1)


Additional Information