Document Detail


Aldose reductase is implicated in high glucose-induced oxidative stress in mouse embryonic neural stem cells.
MedLine Citation:
PMID:  17727625     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Oxidative stress caused by hyperglycemia is one of the key factors responsible for maternal diabetes-induced congenital malformations, including neural tube defects in embryos. However, mechanisms by which maternal diabetes induces oxidative stress during neurulation are not clear. The present study was aimed to investigate whether high glucose induces oxidative stress in neural stem cells (NSCs), which compose the neural tube during development. We also investigated the mechanism by which high glucose disturbs the growth and survival of NSCs in vitro. NSCs were exposed to physiological d-glucose concentration (PG, 5 mmol/L), PG with l-glucose (25 mmol/L), or high d-glucose concentration (HG, 30 or 45 mmol/l). HG induced reactive oxygen species production and mRNA expression of aldose reductase (AR), which catalyzes the glucose reduction through polyol pathway, in NSCs. Expression of glucose transporter 1 (Glut1) mRNA and protein which regulates glucose uptake in NSCs was increased at early stage (24 h) and became down-regulated at late stage (72 h) of exposure to HG. Inhibition of AR by fidarestat, an AR inhibitor, decreased the oxidative stress, restored the cell viability and proliferation, and reduced apoptotic cell death in NSCs exposed to HG. Moreover, inhibition of AR attenuated the down-regulation of Glut1 expression in NSCs exposed to HG for 72 h. These results suggest that the activation of polyol pathway plays a role in the induction of oxidative stress which alters Glut1 expression and cell cycle in NSCs exposed to HG, thereby resulting in abnormal patterning of the neural tube in embryos of diabetic pregnancy.
Authors:
Jiang Fu; S S W Tay; E A Ling; S T Dheen
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-08-28
Journal Detail:
Title:  Journal of neurochemistry     Volume:  103     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-10-26     Completed Date:  2007-12-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  1654-65     Citation Subset:  IM    
Affiliation:
Molecular Neurobiology Laboratory, Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
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MeSH Terms
Descriptor/Qualifier:
Aldehyde Reductase / physiology*
Animals
Cell Proliferation / drug effects
Cell Survival / drug effects,  physiology
Cells, Cultured
Embryonic Stem Cells / cytology,  drug effects,  enzymology*
Glucose / pharmacology*
Mice
Neurons / drug effects,  enzymology*
Oxidative Stress / drug effects,  physiology*
Chemical
Reg. No./Substance:
50-99-7/Glucose; EC 1.1.1.21/Aldehyde Reductase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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