Human Placental Trophoblast Cells Express α-Tocopherol Transfer Protein

Kaempf-Rotzoll, Daisy E.; Horiguchi, Masaaki; Hashiguchi, Kazunari; Aoki, Junken; Tamai, Hiroshi; Linderkamp, Otwin; Arai, Hiroyuki

doi:10.1053/plac.2002.0966

Cited by 64 publications

(34 citation statements)

References 25 publications

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“…In humans, α -TTP has been demonstrated as being presented in term placenta as well as in early-pregnancy trophoblast [14,24] . Both cyto-and syncytiotrophoblasts are reported to express α -TTP [14,20] .…”

Section: Discussionmentioning

confidence: 99%

“…The α -TTP-specifi c rat monoclonal antihuman antibody used in the current study was prepared by Prof. D. Rotzoll (University of Leipzig, Germany) [14] . Specifi city of the antibody used in this study was determined by staining liver tissue known as positive control for α -TTP and by exchanging the primary antibody with an isotype control antibody [rat immunoglobulin G (IgG)] (Figure 1 A).…”

Section: Antibody Preparationmentioning

confidence: 99%

“…α -Tocopherol transfer protein ( α -TTP), with its high affi nity for α -tocopherol, plays a major role in maintaining adequate plasma α -tocopherol levels [1,13] . While α -TTP was initially described as a cytosolic liver protein [25,26] , it has been identifi ed in pregnant mouse uterus and term human placenta [11,12,14] . Recently, it was shown by our group for the fi rst time that α -TTP was present in fi rst-trimester placenta [24] .…”

Section: Introductionmentioning

confidence: 99%

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Oxidative stress stimulates α-tocopherol transfer protein in human trophoblast tumor cells BeWo

Etzl¹,

Vrekoussis

Kühn

et al. 2012

Journal of Perinatal Medicine

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Abstractα -Tocopherol transfer protein ( α -TTP) has been identifi ed as the major intracellular transport protein for the antioxidant vitamin E ( α -tocopherol). Expression of α -TTP on the reproductive system has been described both in mouse uterus and lately in the human placenta. The aim of this study was to clarify if placental expression of α -TTP can be modifi ed by substances causing oxidative reactions. The human choriocarcinoma cell line BeWo was, therefore, treated with two known pro-oxidants. α -TTP expression was determined with immunocytochemistry and evaluated by applying a semiquantitative score. The presence of pro-oxidants in BeWo cells induced α -TTP expression. We thus hypothesize that stimulation of α -TTP expression by oxidative stress, as this was induced by pro-oxidants, could be part of an antioxidant process occurring in the placenta in the aim of enhancing the supply of α -tocopherol. This process could occur both in normal pregnancies, as well as in pregnancy disorders presented with intensifi ed oxidative stress. In that view, this model is proposed for further oxidative stress studies on trophoblast and placenta, on the grounds of clarifying the role of α -tocopherol in pregnancy physiology and pathophysiology.

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Section: Discussionmentioning

confidence: 99%

Section: Antibody Preparationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Oxidative stress stimulates α-tocopherol transfer protein in human trophoblast tumor cells BeWo

Etzl¹,

Vrekoussis

Kühn

et al. 2012

Journal of Perinatal Medicine

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“…In contrast, in wild-type fetuses, low-dose VE consistently failed to increase a-tocopherol levels in any tissue, which accounts for the absence of any reduction in oxidative DNA damage in þ/þ p53 fetuses. The mechanisms underlying this differential VE disposition in wild-type fetuses are not clear; but, as for the tissue-selective differences, these may include variations in membrane transporters 37,38 and, at least in the liver, metabolism of a-tocopherol by the cytochromes P450 CYP3A4 and CYP4F2, 39,40 which may be expressed the fetus towards the end of gestation. 41,42 The tissue-and p53 genotype-dependent nature of the antioxidative efficacy of low-dose VE may explain, in part, the conflicting published reports of antitumor efficacy of VE for different cancers.…”

Section: In Utero Origins Of Cancer/chen Et Almentioning

confidence: 99%

Reduced tumorigenesis in p53 knockout mice exposed in utero to low‐dose vitamin E

Chen

Squire

Wells

2009

Cancer

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BACKGROUND: The limited antioxidative capacity of the fetus renders it more susceptible to reactive oxygen species (ROS), and possibly to ROS‐mediated cancer initiation or promotion in utero. METHODS: To test this hypothesis, pregnant cancer‐prone p53 knockout mice were prenatally supplemented with a low dietary dose of the antioxidant vitamin E (VE) (0.1% all‐rac‐α‐tocopherol‐acetate), and the homozygous (−/−) and heterozygous (+/‐) p53‐deficient and wild‐type (+/+) offspring were examined for VE levels, oxidative DNA damage, chromosomal stability, cellular viability and postnatal tumorigenesis. RESULTS: In utero exposure to VE reduced spontaneous postnatal tumorigenesis in p53 +/‐ offspring, and increased VE levels and reduced fetal DNA oxidation in some but not all tissues of p53‐deficient fetuses. Survival of VE‐exposed p53 +/‐ offspring at the end of the study was double that of the +/‐ controls (45% vs 23%). In primary culture of skin fibroblasts from VE‐exposed fetuses, VE did not alter chromosomal ploidy, but reduced cell death, indicating that its protective effect did not involve chromosomal stability. CONCLUSIONS: The tissue‐selective increase in fetal VE levels and reduced DNA oxidation, together with a concomitant reduction in postnatal tumorigenesis, suggest that in utero oxidative stress contributes to some postnatal cancers, and the risk can be reduced by maternal dietary supplementation with low‐dose VE. Cancer 2009. © 2009 American Cancer Society.

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“…Further homeostatic control is provided by the fact that TTP's stability in cells is modulated by ubiquitination which, in turn, is regulated by ␣-tocopherol (61). Finally, TTP is also expressed in the brain (25,62) and the placenta (28,39,63). It is likely that in these locations, TTP provides an additional layer of regulation that maintains local ␣-tocopherol sufficiency in the most sensitive tissues, i.e.…”

Section: Discussionmentioning

confidence: 99%

Vitamin E and Phosphoinositides Regulate the Intracellular Localization of the Hepatic α-Tocopherol Transfer Protein

Chung¹,

Ghelfi

Atkinson

et al. 2016

Journal of Biological Chemistry

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␣-Tocopherol (vitamin E) is an essential nutrient for all vertebrates. From the eight naturally occurring members of the vitamin E family, ␣-tocopherol is the most biologically active species and is selectively retained in tissues. The hepatic ␣-tocopherol transfer protein (TTP) preferentially selects dietary ␣-tocopherol and facilitates its transport through the hepatocyte and its secretion to the circulation. In doing so, TTP regulates body-wide levels of ␣-tocopherol. The mechanisms by which TTP facilitates ␣-tocopherol trafficking in hepatocytes are poorly understood. We found that the intracellular localization of TTP in hepatocytes is dynamic and responds to the presence of ␣-tocopherol. In the absence of the vitamin, TTP is localized to perinuclear vesicles that harbor CD71, transferrin, and Rab8, markers of the recycling endosomes. Upon treatment with ␣-tocopherol, TTP-and ␣-tocopherol-containing vesicles translocate to the plasma membrane, prior to secretion of the vitamin to the exterior of the cells. The change in TTP localization is specific to ␣-tocopherol and is time-and dose-dependent. The aberrant intracellular localization patterns of lipid binding-defective TTP mutants highlight the importance of protein-lipid interaction in the transport of ␣-tocopherol. These findings provide the basis for a proposed mechanistic model that describes TTP-facilitated trafficking of ␣-tocopherol through hepatocytes.Vitamin E is a plant-derived lipid that was discovered as a dietary component vital for female fertility in rodents (1) and for neuronal health in humans (2). Eight vitamin E forms are synthesized by plants, differing in the degree of methylation of the chromanol ring and the saturation of the isoprenoid side chain (3). Of the eight naturally occurring forms of vitamin E, ␣-tocopherol exhibits the most potent biological activity in preventing deficiency-induced reproductive failure in rodents (4, 5). ␣-Tocopherol's efficacy in scavenging free radicals (i.e. functioning as an antioxidant) is thought to underlie its critical roles in health (6 -8), but additional redox-independent actions have been recently proposed (9).The major regulator of vitamin E status is the ␣-tocopherol transfer protein (TTP), 2 and mutations in the TTPA gene cause heritable vitamin E deficiency. In humans, mutations in the TTPA gene cause systemic vitamin E deficiency accompanied by neurological compromise, primarily spinocerebellar ataxia (10 -17). Patients afflicted with this disorder (ataxia with vitamin E deficiency; OMIM 277460) present with debilitating neurodegeneration, the severity of which depends on the specific mutation's effect on TTP's biochemical activity (18,19). Lifelong vitamin E supplementation can delay or reverse disease progression, especially when patients are treated in earlier stages (20,21). Disruption of the TtpA gene in mice recapitulated the human ataxia with vitamin E deficiency disorder (22).TTP is expressed at high levels in parenchymal cells of the liver (23, 24), but low level expression has b...

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Human Placental Trophoblast Cells Express α-Tocopherol Transfer Protein

Cited by 64 publications

References 25 publications

Oxidative stress stimulates α-tocopherol transfer protein in human trophoblast tumor cells BeWo

Oxidative stress stimulates α-tocopherol transfer protein in human trophoblast tumor cells BeWo

Reduced tumorigenesis in p53 knockout mice exposed in utero to low‐dose vitamin E

Vitamin E and Phosphoinositides Regulate the Intracellular Localization of the Hepatic α-Tocopherol Transfer Protein

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