The role of α-tocopherol in motor hypofunction with aging in α-tocopherol transfer protein knockout mice as assessed by oxidative stress biomarkers

Yoshida, Yasukazu; Itoh, Nanako; Hayakawa, Mieko; Habuchi, Yoko; Saito, Yoshiro; Tsukamoto, Yoshitane; Cynshi, Osamu; Jishage, Kou Ichi; Arai, Hiroyuki; Niki, Etsuo

doi:10.1016/j.jnutbio.2008.10.006

Cited by 22 publications

(18 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line with α-tocopherol's established antioxidant activity (Burton et al, 1983, Burton and Traber, 1990, Traber and Atkinson, 2007), vitamin E deficiency in Ttpa -/- mice is accompanied by significant increases in the levels of oxidative stress markers, such as TBARS (Yokota et al, 2001), F2-isoprostanes (Terasawa et al, 2000) and tHODEs (Yoshida et al, 2010). To complement these signatures of oxidative stress, we investigated the levels of 3-nitrotyrosine (3-NT).…”

Section: Resultsmentioning

confidence: 82%

“…In line with vitamin E's established function as an antioxidant, increased levels of oxidative stress markers have been described in the vitamin E depleted Ttpa -/- mice. Specifically, altered levels of TBARS, 4-HNE adducts, t-IsoPGF 2α and t-HODE and glutathione were demonstrated in the cerebellum, cortex, and spinal cord of these mice as compared to vitamin E sufficient animals (Yokota et al, 2001, Gohil et al, 2010, Yoshida et al, 2010). These changes are thought to cause specific cellular dysfunctions such as defective retrograde axonal transport (Southam et al, 1991) and impaired mitochondrial function in affected neurons (Thomas et al, 1993, Pillai et al, 1994), which eventually lead to axonal degeneration (Koeppen, 2005).…”

Section: Discussionmentioning

confidence: 88%

See 1 more Smart Citation

Vitamin E is essential for Purkinje neuron integrity

et al. 2014

View full text Add to dashboard Cite

Alpha-tocopherol (vitamin E) is an essential dietary antioxidant with important neuroprotective functions. Alpha-tocopherol deficiency manifests primarily in neurological pathologies, notably cerebellar dysfunctions such as spinocerebellar ataxia. To study the roles of α-tocopherol in the cerebellum, we used the Ttpa-/- mice which lack the tocopherol transfer protein (TTP) and are a faithful model of vitamin E deficiency and oxidative stress. When fed vitamin E deficient diet, Ttpa-/- mice had un-detectable levels of α-tocopherol in plasma and several brain regions. Dietary supplementation with α-tocopherol normalized plasma levels of the vitamin, but only modestly increased its levels in the cerebellum and prefrontal cortex, indicating a critical function of brain TTP. Vitamin E deficiency caused an increase in cerebellar oxidative stress evidenced by increased protein nitrosylation, which was prevented by dietary supplementation with the vitamin. Concomitantly, vitamin E deficiency precipitated cellular atrophy and diminished dendritic branching of Purkinje neurons, the predominant output regulator of the cerebellar cortex. The anatomic decline induced by vitamin E deficiency was paralleled by behavioral deficits in motor coordination and cognitive functions that were normalized upon vitamin E supplementation. These observations underscore the essential role of vitamin E and TTP in maintaining CNS function, and support the notion that α-tocopherol supplementation may comprise an effective intervention in oxidative stress-related neurological disorders.

show abstract

Section: Resultsmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 88%

Vitamin E is essential for Purkinje neuron integrity

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Since analysis of the NPC-affected tissue is impractical, a sensitive circulating indicator of oxidative stress may be the appropriate biomarker in this case. Circulating unsaturated lipid peroxidation products, such as HETEs and isoprostanes ( 88,89 ), and hydroxylated cholesterol metabolites ( 85 ) may serve as the proper biomarker for these purposes. Clearly, there is a dire need to better defi ne and optimize the most suitable plasma marker for oxidation status and to streamline its applicability for routine clinical use.…”

Section: Figmentioning

confidence: 99%

Altered vitamin E status in Niemann-Pick type C disease

Ulatowski

Parker

Davidson

et al. 2011

Journal of Lipid Research

View full text Add to dashboard Cite

“…Tissue levels of α-tocopherol are reported to be normal in heterozygote α-TTP−/+ mice. In contrast, mice with a homozygous deletion in α-TTP (α-TTP−/− mice) have dramatically reduced blood and tissue levels of α-tocopherol (9) and exhibit increased oxidative stress as they age (10). …”

Section: Introductionmentioning

confidence: 99%

Evaluation of long-term vitamin E insufficiency or excess on bone mass, density, and microarchitecture in rodents

Iwaniec

Turner

et al. 2013

Free Radical Biology and Medicine

View full text Add to dashboard Cite

High dietary α-tocopherol levels reportedly result in osteopenia in growing rats, while α-tocopherol deficiency in α-tocopherol transfer protein knockout (α-TTP KO) mice results in increased cancellous bone mass. Since osteoporosis is a disease associated primarily with aging, we hypothesized that age-related bone loss would be attenuated in α-TTP KO mice. Cancellous and cortical bone mass and microarchitecture were assessed using dual energy x-ray absorptiometry and micro-computed tomography in 2-year-old α-TTP KO and wildtype (WT) male and female mice fed DL-α-tocopherol acetate. In contrast to our expectations, differences in cancellous bone were not detected between WT and α-TTP KO mice in either gender and α-TTP KO males had lower (p < 0.05) cortical bone mass than WT males. We therefore evaluated bone mass, density and microarchitecture in proximal femur of skeletally mature (8.5-months-old) male Sprague-Dawley rats fed diets containing low (15 IU/kg), adequate (75 IU/kg), or high (500 IU/kg diet) DL-α-tocopherol acetate for 13 weeks. Low dietary α-tocopherol did not increase bone mass. Furthermore, no reductions in cancellous or cortical bone mass were detected with high dietary α-tocopherol. Failure to detect increased bone mass in aged α-TTP KO mice or bone changes in skeletally mature rats fed either low or high levels of α-tocopherol does not support the hypothesis that α-tocopherol has a negative impact on bone mass, density or microarchitecture in rodents.

show abstract

The role of α-tocopherol in motor hypofunction with aging in α-tocopherol transfer protein knockout mice as assessed by oxidative stress biomarkers

Cited by 22 publications

References 28 publications

Vitamin E is essential for Purkinje neuron integrity

Vitamin E is essential for Purkinje neuron integrity

Altered vitamin E status in Niemann-Pick type C disease

Evaluation of long-term vitamin E insufficiency or excess on bone mass, density, and microarchitecture in rodents

Contact Info

Product

Resources

About