Source:http://linkedlifedata.com/resource/pubmed/id/15120582
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1-2
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| pubmed:dateCreated |
2004-5-3
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| pubmed:abstractText |
Glucose is the brain's major energy source; therefore, loss of neuronal cells is a potential consequence of hypoglycaemia. Since apoptosis is a major mechanism of neuronal loss following a range of insults, we explored potent anti-apoptotic systems (IGF-I and bcl-2) as means of enhancing neuronal survival in the face of glucose deprivation. Human neuroblastoma cells (SH-SY5Y, SHEP and SHEP-bcl-2) were exposed to low glucose as a model of glucopenia-induced neuronal damage. Administration of IGF-I and/or over-expression of the survival gene bcl-2 were exploited to attempt to limit neuronal loss. Neuronal survival mechanisms and interactions between these systems were investigated. Low glucose (0.25-2.5 mM) adversely affected cell growth and survival; however, IGF-I ameliorated these outcomes. Over-expression of bcl-2 blunted low glucose-induced apoptosis and up-regulated IGF-I receptor, with the effect of IGF-I addition being negligible on apoptosis, while significantly enhancing mitochondrial activity. In SH-SY5Y cells, IGF-I significantly changed >two-fold mRNA levels of the apoptosis-related genes gadd45, fas, iNOS, NFkB, TRAIL, without further affecting bcl-2 expression. In low glucose, IGF-I acutely enhanced glucose transport and translocation of GLUT1 protein to the cell membrane. GLUT1 mRNA expression was up-regulated by both IGF-I and bcl-2. The potent anti-apoptotic systems IGF-I and bcl-2 are both thus able to enhance cell survival in a glucose-deprived human neuronal model. Although we clearly show evidence of positive cross-talk via bcl-2 modulation of IGF-I receptor, IGF-I also has enhancing effects on mitochondrial function outside the bcl-2 pathway. The common effect of both systems on enhancement of GLUT-1 expression suggests that this is a key mechanism for enhanced survival. These studies also point to the potential use of IGF-I therapy in prevention or amelioration of hypoglycaemic brain injury.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Serum-Free,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose Transporter Type 1,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Iodine Isotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Monosaccharide Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SLC2A1 protein, human
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
0006-8993
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
29
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| pubmed:volume |
1009
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
40-53
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:15120582-Analysis of Variance,
pubmed-meshheading:15120582-Apoptosis,
pubmed-meshheading:15120582-Biological Transport,
pubmed-meshheading:15120582-Blotting, Northern,
pubmed-meshheading:15120582-Blotting, Western,
pubmed-meshheading:15120582-Cell Count,
pubmed-meshheading:15120582-Cell Division,
pubmed-meshheading:15120582-Cell Line, Tumor,
pubmed-meshheading:15120582-Cell Survival,
pubmed-meshheading:15120582-Culture Media, Serum-Free,
pubmed-meshheading:15120582-Dose-Response Relationship, Drug,
pubmed-meshheading:15120582-Drug Interactions,
pubmed-meshheading:15120582-Enzyme Inhibitors,
pubmed-meshheading:15120582-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:15120582-Gene Expression,
pubmed-meshheading:15120582-Glucose,
pubmed-meshheading:15120582-Glucose Transporter Type 1,
pubmed-meshheading:15120582-Humans,
pubmed-meshheading:15120582-Insulin-Like Growth Factor I,
pubmed-meshheading:15120582-Iodine Isotopes,
pubmed-meshheading:15120582-Mitochondria,
pubmed-meshheading:15120582-Monosaccharide Transport Proteins,
pubmed-meshheading:15120582-Neuroblastoma,
pubmed-meshheading:15120582-Neurons,
pubmed-meshheading:15120582-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:15120582-Protein Binding,
pubmed-meshheading:15120582-Proto-Oncogene Proteins,
pubmed-meshheading:15120582-Signal Transduction,
pubmed-meshheading:15120582-Time Factors,
pubmed-meshheading:15120582-Translocation, Genetic
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| pubmed:year |
2004
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| pubmed:articleTitle |
Neuronal protection from glucose deprivation via modulation of glucose transport and inhibition of apoptosis: a role for the insulin-like growth factor system.
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| pubmed:affiliation |
Centre for Hormone Research, Murdoch Childrens Research Institute, Royal Children's Hospital, Flemington Road, Parkville 3052, Victoria, Australia. vince.russo@mcri.edu.au
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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