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Hypoxanthine-xanthine oxidase (HX/XO) downregulates GLUT-1 transcription via SIRT1 resulting in decreased glucose uptake in human placenta.
MedLine Citation:
PMID:  22266962     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Appropriate fetal growth and development is dependent on adequate placental glucose uptake. Oxidative stress regulates glucose uptake in various tissues. The effect of oxidative stress on placenta glucose transport is not known. Thus, the aim of this study was to determine the effect of oxidative stress on glucose uptake and glucose transporters in human placenta. Human placenta was incubated with in the absence or presence of 0.5 mM HX + 15 mU/ml XO (HX/XO) for 24 h. Gene and protein expression of the glucose transporters (GLUTs) were analysed by quantitative RT-PCR (qRT-PCR) and Western blotting, respectively. Glucose uptake was measured using radiolabelled (14C) glucose. HX/XO significantly decreased GLUT-1 gene and protein expression and resultant glucose uptake. There was no effect of the antioxidants N-acetyl-cysteine (NAC), catalase and superoxide dismutase (SOD), or the NF-κB inhibitor BAY 11-0782 on HX/XO-induced decrease in glucose uptake. However, HX/XO treatment significantly decreased both gene and protein expression of SIRT1. In the presence of the SIRT1 activator resveratrol, the decrease in GLUT-1 expression and glucose uptake mediated by HX/XO was abolished. Collectively, the data presented here demonstrate that oxidative stress reduces placental glucose uptake and GLUT-1 expression by a SIRT1 dependent mechanism.
Authors:
Martha Lappas; Sofianos Andrikopoulos; Michael Permezel
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-19
Journal Detail:
Title:  The Journal of endocrinology     Volume:  -     ISSN:  1479-6805     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375363     Medline TA:  J Endocrinol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
M Lappas, Department of Obstetrics and Gynaecology, University of Melbourne, HEIDELBERG, Australia.
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