Gene expression profile of oxidant stress and neurodegeneration in transgenic mice deficient in α-tocopherol transfer protein

Kishorchandra Gohil, Bettina C. Schock, Abhishek A. Chakraborty, Yuko Terasawa, Jacob Raber, Robert V. Farese, Lester Packer, Carroll E. Cross, Maret G. Traber

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

Alpha-tocopherol transfer protein (TTP) regulates the retention and secretion of α-tocopherol (α-T) by the liver. Deletion of the TTP gene (Ttpa) in mice results in systemic deficiency of α-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-α and repression of synuclein-β genes was detected in Ttpa-/- cortex. This may predispose Ttpa-/- cortex to increased formation of synuclein-α 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-α 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.

Original languageEnglish (US)
Pages (from-to)1343-1354
Number of pages12
JournalFree Radical Biology and Medicine
Volume35
Issue number11
DOIs
StatePublished - Dec 1 2003
Externally publishedYes

Fingerprint

Tocopherols
Transcriptome
Oxidants
Gene expression
Liver
Transgenic Mice
Synucleins
Genes
Proteins
MAP Kinase Kinase 3
Antioxidant Response Elements
Myelin Proteins
Lewy Bodies
Messenger RNA
Retinoic Acid Receptors
Neuronal Plasticity
Gene encoding
Cell proliferation
Ataxia
Protein Kinase C

Keywords

  • Antioxidant
  • Anxiety
  • Free radicals
  • Long-term potentiation
  • Neurodegeneration
  • Oligonucleotide arrays
  • Synapse
  • Vitamin E

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Gene expression profile of oxidant stress and neurodegeneration in transgenic mice deficient in α-tocopherol transfer protein. / Gohil, Kishorchandra; Schock, Bettina C.; Chakraborty, Abhishek A.; Terasawa, Yuko; Raber, Jacob; Farese, Robert V.; Packer, Lester; Cross, Carroll E.; Traber, Maret G.

In: Free Radical Biology and Medicine, Vol. 35, No. 11, 01.12.2003, p. 1343-1354.

Research output: Contribution to journalArticle

Gohil, Kishorchandra ; Schock, Bettina C. ; Chakraborty, Abhishek A. ; Terasawa, Yuko ; Raber, Jacob ; Farese, Robert V. ; Packer, Lester ; Cross, Carroll E. ; Traber, Maret G. / Gene expression profile of oxidant stress and neurodegeneration in transgenic mice deficient in α-tocopherol transfer protein. In: Free Radical Biology and Medicine. 2003 ; Vol. 35, No. 11. pp. 1343-1354.
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AU - Terasawa, Yuko

AU - Raber, Jacob

AU - Farese, Robert V.

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AU - Cross, Carroll E.

AU - Traber, Maret G.

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