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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2003-12-3
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pubmed:abstractText |
Alpha-tocopherol transfer protein (TTP) regulates the retention and secretion of alpha-tocopherol (alpha-T) by the liver. Deletion of the TTP gene (Ttpa) in mice results in systemic deficiency of alpha-T and neurological dysfunctions described in patients with mutated Ttpa. We have explored genome-wide changes in mRNAs from brain cortex and liver of Ttpa-deficient (Ttpa(-/-)) mice and wild-type (Ttpa(+/+)) mice. Selective inductions of genes regulated by antioxidant response elements were detected in Ttpa(-/-) livers compared to Ttpa(+/+) livers, suggesting increased oxidant stress in Ttpa(-/-) livers. The activation of cell proliferation pathways in Ttpa(-/-) livers was indicated by the induction of genes that encode growth factor-binding proteins, mitogen-activated protein kinase kinase 3, and apoptosis inhibitor 6. The induction of synuclein-alpha and repression of synuclein-beta genes was detected in Ttpa(-/-) cortex. This may predispose Ttpa(-/-) cortex to increased formation of synuclein-alpha aggregates and Lewy body, often associated with oxidant stress. Cortex of Ttpa(-/-) mice revealed repression of genes encoding synaptic proteins, protein kinase C family members, and myelin proteins. A 13-fold decrease in the expression of retinoic acid receptor-related orphan receptor-alpha mRNA predicts staggerer-like phenotype (ataxia and deficits of motor coordination) of Ttpa(-/-) mice. The repression of specific genes that determine synaptic plasticity and neuronal development may account for suppressed electrophysiological activities of cortex and impaired behavior in Ttpa(-/-) mice.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/MAP2K3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Map2k3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Receptor Subfamily 1...,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Retinoic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-tocopherol transfer protein
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0891-5849
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
35
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1343-54
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14642382-Animals,
pubmed-meshheading:14642382-Brain,
pubmed-meshheading:14642382-Carrier Proteins,
pubmed-meshheading:14642382-Cell Division,
pubmed-meshheading:14642382-DNA,
pubmed-meshheading:14642382-Female,
pubmed-meshheading:14642382-Gene Deletion,
pubmed-meshheading:14642382-Gene Expression Regulation,
pubmed-meshheading:14642382-Liver,
pubmed-meshheading:14642382-MAP Kinase Kinase 3,
pubmed-meshheading:14642382-Male,
pubmed-meshheading:14642382-Maze Learning,
pubmed-meshheading:14642382-Mice,
pubmed-meshheading:14642382-Mice, Inbred C57BL,
pubmed-meshheading:14642382-Mice, Transgenic,
pubmed-meshheading:14642382-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:14642382-Models, Biological,
pubmed-meshheading:14642382-Myelin Sheath,
pubmed-meshheading:14642382-Neurodegenerative Diseases,
pubmed-meshheading:14642382-Nuclear Receptor Subfamily 1, Group F, Member 1,
pubmed-meshheading:14642382-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:14642382-Oxidants,
pubmed-meshheading:14642382-Protein Kinase C,
pubmed-meshheading:14642382-Protein-Tyrosine Kinases,
pubmed-meshheading:14642382-RNA,
pubmed-meshheading:14642382-RNA, Messenger,
pubmed-meshheading:14642382-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:14642382-Receptors, Retinoic Acid,
pubmed-meshheading:14642382-Trans-Activators,
pubmed-meshheading:14642382-Transcription Factors
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pubmed:year |
2003
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pubmed:articleTitle |
Gene expression profile of oxidant stress and neurodegeneration in transgenic mice deficient in alpha-tocopherol transfer protein.
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pubmed:affiliation |
Center for Comparative Respiratory and Medicine, Department of Internal Medicine, University of California, Davis, CA 95616, USA. kgohil@ucdavis.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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