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Maret G Traber - One of the best experts on this subject based on the ideXlab platform.
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Vitamin E is Necessary to Protect Neural Crest Cells in Developing Zebrafish Embryos
Current Developments in Nutrition, 2020Co-Authors: Brian Head, Robyn L Tanguay, Chrissa Kioussi, Maret G TraberAbstract:Abstract Objectives Vitamin E (VitE) deficiency causes vertebrate embryonic lethality. The Alpha-Tocopherol Transfer Protein (Ttpa) likely regulates VitE distribution in the early zebrafish embryo because Ttpa knockdown causes impaired nervous system development and embryonic death by 15–18 hours post-fertilization (hpf). We propose that VitE is necessary for normal brain and peripheral nervous system development. Methods Zebrafish embryos are obtained from adults fed either VitE sufficient (E+) or deficient (E–) diets for at least 80 days. Embryos at 12 and 24 hpf are subjected to RNA whole mount in situ hybridization (WISH). RNA is also collected from embryos at 12, 18 and 24 hpf for RT-qPCR of specific targets. Results At 12 hpf, the midbrain-hindbrain boundary and otic placodes are malformed in E– embryos, as shown by Pax2a expression. Similarly, Sox10 expression shows that E– embryos lack clear neural plate borders. Nonetheless, in 12 hpf E + and E− embryos Ttpa is localized similarly throughout the nervous system. Pax2a expression initiates collagen formation in the developing notochord. Collagen genes, col2a1a and col9a2, expression patterns showed abnormal notochord structures in 24 hpf E– embryos. At 24 hpf in E + embryos, Sox10 expressing-neural crest cells are localized both in the central nervous system and dorsal root ganglia (DRG), while the Sox10 signal is diminished in E– embryos in both the DRG and early enteric nervous system. At 24 hpf, Ttpa expression outlines the brain ventricle borders; critically E– embryos show reduced Ttpa signal and impaired ventricle closing. Gene expression by qPCR will be used to confirm these results. Conclusions This VitE deficient embryo model suggests that the carefully programmed development of the nervous system is distorted due to lack of adequate VitE. Thus, Ttpa and VitE are critical molecules for neural plate and neural tube formation, and neural crest cell migration. Funding Sources The authors received no specific funding for this work.
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Modulation of ozone-sensitive genes in Alpha-Tocopherol Transfer Protein null mice.
Inhalation Toxicology, 2009Co-Authors: Vihas T. Vasu, Brad A. Hobson, Carroll E. Cross, Maret G Traber, Saji Oommen, Giuseppe Valacchi, Jason P. Eiserich, Scott W. Leonard, Kishorchandra GohilAbstract:Alpha-Tocopherol Transfer Protein (ATTP) null mice (ATTP−/−) have a systemic Alpha-Tocopherol (AT) deficiency, with their lung AT levels being
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Alpha-Tocopherol Transfer Protein (α-TTP): Insights from Alpha-Tocopherol Transfer Protein Knockout Mice
Nutrition Research and Practice, 2007Co-Authors: Maret G TraberAbstract:Alpha-Tocopherol Transfer Protein (α-TTP) is a liver cytosolic transport Protein that faciliates α-tocopherol (α-T) Transfer into liver secreted plasma lipoProteins. Genetic defects in α-TTP, like dietary vitamin E deficiency, are associated with infertility, muscular weakness and neurological disorders. Both human and α-TTP deficient (α-TTP-/-) mice exhibit severe plasma and tissue vitamin E deficiency that can be attenuated by sufficient dietary α-T supplementations. In this review, we summarize the literature concerning studies utilizing the α-TTP-/- mice. Levels of vitamin E in the α-TTP-/- mice do not appear to be directly related to the amounts of dietary α-T or to the levels of α-TTP Protein in tissues. The α-TTP-/- mice appear to present a good model for investigating the specific role of α-T in tissue vitamin E metabolism. Furthermore, α-TTP-/- mice appear to be useful to elucidate functions of α-TTP beyond its well recognized functions of Transferring α-T from liver to plasma lipoProtein fractions.
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Vitamin E Regulatory Mechanisms
Annual Review of Nutrition, 2007Co-Authors: Maret G TraberAbstract:Dietary and supplemental vitamin E is absorbed and delivered to the liver, but of the various antioxidants with vitamin E activity, only Alpha-Tocopherol is preferentially recognized by the Alpha-Tocopherol Transfer Protein (alpha-TTP) and is Transferred to plasma, while the other vitamin E forms (e.g., gamma-tocopherol or tocotrienols) are removed from the circulation. Hepatic alpha-TTP is required to maintain plasma and tissue Alpha-Tocopherol concentrations. The liver is the master regulator of the body's vitamin E levels in that it not only controls Alpha-Tocopherol concentrations, but also appears to be the major site of vitamin E metabolism and excretion. Vitamin Es are metabolized similarly to xenobiotics; they are initially omega-oxidized by cytochrome P450s, undergo several rounds of beta-oxidation, and then are conjugated and excreted. As a result of these various mechanisms, liver Alpha-Tocopherol and other vitamin E concentrations are closely regulated; thus, any potential adverse vitamin E effects are limited.
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Vitamin E Modulates Inflammatory Responses Induced by Cigarette Smoke (CS) Exposure in alpha -Tocopherol Transfer Protein (TTP) Null Mice
The FASEB Journal, 2006Co-Authors: Vihas T. Vasu, Kishorchandra Gohil, Maret G Traber, Giuseppe Valacchi, Scott W. Leonard, Hnin Hnin Aung, Carroll E. CrossAbstract:CS induced pulmonary inflammatory responses have been reported to be associated with oxidative stress and decreased levels of vitamin E (Alpha-Tocopherol, a-T), possibly due to increased utilizatio...
Carroll E. Cross - One of the best experts on this subject based on the ideXlab platform.
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Modulation of ozone-sensitive genes in Alpha-Tocopherol Transfer Protein null mice.
Inhalation Toxicology, 2009Co-Authors: Vihas T. Vasu, Brad A. Hobson, Carroll E. Cross, Maret G Traber, Saji Oommen, Giuseppe Valacchi, Jason P. Eiserich, Scott W. Leonard, Kishorchandra GohilAbstract:Alpha-Tocopherol Transfer Protein (ATTP) null mice (ATTP−/−) have a systemic Alpha-Tocopherol (AT) deficiency, with their lung AT levels being
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Genome-Wide Screening of Alpha-Tocopherol Sensitive Genes in Heart Tissue from Alpha-Tocopherol Transfer Protein Null Mice (ATTP−/−)
FEBS Letters, 2007Co-Authors: Vihas T. Vasu, Brad A. Hobson, Kishorchandra Gohil, Carroll E. CrossAbstract:Abstract Alpha-Tocopherol Transfer Protein (ATTP) null mice (ATTP−/−) have a systemic deficiency of Alpha-Tocopherol (AT). The heart AT levels of ATTP−/− are
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Genome‐wide screening of alpha‐tocopherol sensitive genes in heart tissue from alpha‐tocopherol Transfer Protein null mice (ATTP−/−)
FEBS Letters, 2007Co-Authors: Vihas T. Vasu, Brad A. Hobson, Kishorchandra Gohil, Carroll E. CrossAbstract:Alpha tocopherol Transfer Protein (ATTP) null mice (ATTP−/−) have a systemic deficiency of Alpha-Tocopherol (AT). The heart AT levels of ATTP−/− are
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Vitamin E Modulates Inflammatory Responses Induced by Cigarette Smoke (CS) Exposure in alpha -Tocopherol Transfer Protein (TTP) Null Mice
The FASEB Journal, 2006Co-Authors: Vihas T. Vasu, Kishorchandra Gohil, Maret G Traber, Giuseppe Valacchi, Scott W. Leonard, Hnin Hnin Aung, Carroll E. CrossAbstract:CS induced pulmonary inflammatory responses have been reported to be associated with oxidative stress and decreased levels of vitamin E (Alpha-Tocopherol, a-T), possibly due to increased utilizatio...
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α-tocopherol Transfer Protein deficiency in mice causes multi-organ deregulation of gene networks and behavioral deficits with age
Annals of the New York Academy of Sciences, 2004Co-Authors: Kishorchandra Gohil, Carroll E. Cross, Bettina C. Schock, Lester Packer, Roy Godzdanker, Erin O’roark, Ramesh R. Kaini, Maret G TraberAbstract:: Functions of Alpha-Tocopherol (alpha-T) in vivo, other than those for fertility in females, are intensely debated. The discovery of alpha-T deficiency in patients with ataxia (AVED) followed by the identification of mutations in the gene encoding Alpha-Tocopherol Transfer Protein (TTP) in AVED patients demonstrates an essential role of alpha-T and TTP for normal neurological function. alpha-T molecular targets that account for alpha-T-sensitive neurological dysfunction remain to be discovered. We have used high-density oligonucleotide arrays to search for putative alpha-T-sensitive genes in the CNS and other tissues in an in vivo model of alpha-T deficiency imposed at birth by the deletion of the TTP gene in mice. Repression of genes affecting synaptic function and myelination and induction of genes for neurodegeneration in the motor cortex of alpha-T-deficient mice were identified. The expression of retinoic acid-related orphan receptor alpha (ROR-alpha) was repressed in the cortex and adrenal glands of TTP-deficient mice. Deficiency of ROR-alpha causes ataxia in mice and may account for ataxia in AVED patients. These observations suggest that some of the actions of alpha-T are mediated by the transcription factor ROR-alpha. The behavior of young TTP-null mice was essentially normal, but older mice showed inactivity, ataxia, and memory dysfunction. mRNA profiles of old alpha-T-deficient cerebral cortices are compatible with repressed activity of oligodendrocytes and astrocytes. In conclusion, gene-expression profiling studies have identified novel alpha-T-modulated genes and cells in the CNS that may be causatively linked with delayed neurodegeneration and age-related decline in behavioral repertoires.
Kishorchandra Gohil - One of the best experts on this subject based on the ideXlab platform.
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Modulation of ozone-sensitive genes in Alpha-Tocopherol Transfer Protein null mice.
Inhalation Toxicology, 2009Co-Authors: Vihas T. Vasu, Brad A. Hobson, Carroll E. Cross, Maret G Traber, Saji Oommen, Giuseppe Valacchi, Jason P. Eiserich, Scott W. Leonard, Kishorchandra GohilAbstract:Alpha-Tocopherol Transfer Protein (ATTP) null mice (ATTP−/−) have a systemic Alpha-Tocopherol (AT) deficiency, with their lung AT levels being
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Genome-Wide Screening of Alpha-Tocopherol Sensitive Genes in Heart Tissue from Alpha-Tocopherol Transfer Protein Null Mice (ATTP−/−)
FEBS Letters, 2007Co-Authors: Vihas T. Vasu, Brad A. Hobson, Kishorchandra Gohil, Carroll E. CrossAbstract:Abstract Alpha-Tocopherol Transfer Protein (ATTP) null mice (ATTP−/−) have a systemic deficiency of Alpha-Tocopherol (AT). The heart AT levels of ATTP−/− are
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Genome‐wide screening of alpha‐tocopherol sensitive genes in heart tissue from alpha‐tocopherol Transfer Protein null mice (ATTP−/−)
FEBS Letters, 2007Co-Authors: Vihas T. Vasu, Brad A. Hobson, Kishorchandra Gohil, Carroll E. CrossAbstract:Alpha tocopherol Transfer Protein (ATTP) null mice (ATTP−/−) have a systemic deficiency of Alpha-Tocopherol (AT). The heart AT levels of ATTP−/− are
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Vitamin E Modulates Inflammatory Responses Induced by Cigarette Smoke (CS) Exposure in alpha -Tocopherol Transfer Protein (TTP) Null Mice
The FASEB Journal, 2006Co-Authors: Vihas T. Vasu, Kishorchandra Gohil, Maret G Traber, Giuseppe Valacchi, Scott W. Leonard, Hnin Hnin Aung, Carroll E. CrossAbstract:CS induced pulmonary inflammatory responses have been reported to be associated with oxidative stress and decreased levels of vitamin E (Alpha-Tocopherol, a-T), possibly due to increased utilizatio...
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α-tocopherol Transfer Protein deficiency in mice causes multi-organ deregulation of gene networks and behavioral deficits with age
Annals of the New York Academy of Sciences, 2004Co-Authors: Kishorchandra Gohil, Carroll E. Cross, Bettina C. Schock, Lester Packer, Roy Godzdanker, Erin O’roark, Ramesh R. Kaini, Maret G TraberAbstract:: Functions of Alpha-Tocopherol (alpha-T) in vivo, other than those for fertility in females, are intensely debated. The discovery of alpha-T deficiency in patients with ataxia (AVED) followed by the identification of mutations in the gene encoding Alpha-Tocopherol Transfer Protein (TTP) in AVED patients demonstrates an essential role of alpha-T and TTP for normal neurological function. alpha-T molecular targets that account for alpha-T-sensitive neurological dysfunction remain to be discovered. We have used high-density oligonucleotide arrays to search for putative alpha-T-sensitive genes in the CNS and other tissues in an in vivo model of alpha-T deficiency imposed at birth by the deletion of the TTP gene in mice. Repression of genes affecting synaptic function and myelination and induction of genes for neurodegeneration in the motor cortex of alpha-T-deficient mice were identified. The expression of retinoic acid-related orphan receptor alpha (ROR-alpha) was repressed in the cortex and adrenal glands of TTP-deficient mice. Deficiency of ROR-alpha causes ataxia in mice and may account for ataxia in AVED patients. These observations suggest that some of the actions of alpha-T are mediated by the transcription factor ROR-alpha. The behavior of young TTP-null mice was essentially normal, but older mice showed inactivity, ataxia, and memory dysfunction. mRNA profiles of old alpha-T-deficient cerebral cortices are compatible with repressed activity of oligodendrocytes and astrocytes. In conclusion, gene-expression profiling studies have identified novel alpha-T-modulated genes and cells in the CNS that may be causatively linked with delayed neurodegeneration and age-related decline in behavioral repertoires.
Udo Jeschke - One of the best experts on this subject based on the ideXlab platform.
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Alpha tocopherol Transfer Protein (αTTP) is expressed in endometrial carcinoma and is correlated with FIGO stage and 5-year survival
Journal of Cancer Research and Clinical Oncology, 2017Co-Authors: Sabine Heublein, Thomas Vrekoussis, Ronny Etzl, Daisy Rotzoll, Christina Kuhn, Gesine Faigle, Iordanis Navrozoglou, Theodore Stefos, Antonis Makrigiannakis, Udo JeschkeAbstract:Background Increased oxidative stress plays an important role in cancer development. Vitamin E is considered a potent anti-oxidant and its Transfer Protein αTTP facilitates its cellular delivery. We hypothesize that αTTP could be present in and have an impact on endometrial cancer. Materials and methods Ishikawa endometrial cancer cells were treated with BSO and AAPH to mimick oxidative stress conditions. αTTP was detected by immunocytochemistry and western blot. αΤΤP expression was then assessed in 191 endometrioid endometrial carcinomas. Immunopositivity was correlated with grade, FIGO stage, and 5-year survival. Immuno-reactivity was assessed with a semi-quantitative score. Results AAPH- and BSO-induced αTTP expression in Ishikawa cells. Immunohistochemical assessment of the 191 endometrial cancer cases showed that αTTP expression correlated with FIGO stage ( p = 0.014) but not with grade. Five-year survival was significantly better in cases of lower αTTP expression compared to cases with higher expression ( p = 0.041). Conclusions The current results show that αTTP plays a role in endometrial carcinoma. Possibly endometrial cancer cells attempt to protect themselves from increasing oxidative stress by up-regulating αTTP. Selective molecular interventions targeting oxidative stress escape strategies, e.g., by overexpression of αTTP, could, therefore, allow oxidative stress to damage cancer cell membranes and thus restrict cancer progression.
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Alpha tocopherol Transfer Protein (αTTP) is expressed in endometrial carcinoma and is correlated with FIGO stage and 5-year survival
Journal of Cancer Research and Clinical Oncology, 2017Co-Authors: Sabine Heublein, Thomas Vrekoussis, Ronny Etzl, Daisy Rotzoll, Christina Kuhn, Gesine Faigle, Iordanis Navrozoglou, Theodore Stefos, Antonis Makrigiannakis, Udo JeschkeAbstract:Background Increased oxidative stress plays an important role in cancer development. Vitamin E is considered a potent anti-oxidant and its Transfer Protein αTTP facilitates its cellular delivery. We hypothesize that αTTP could be present in and have an impact on endometrial cancer.
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Oxidative stress stimulates α-tocopherol Transfer Protein in human trophoblast tumor cells BeWo.
Journal of Perinatal Medicine, 2012Co-Authors: Ronny Etzl, Thomas Vrekoussis, Christina Kuhn, Antonis Makrigiannakis, Udo Jeschke, Sandra Schulze, Johannes Pöschl, Daisy E. RotzollAbstract:Alpha-Tocopherol Transfer Protein (alpha-TTP) has been identified as the major intracellular transport Protein for the antioxidant vitamin E (Alpha-Tocopherol). Expression of alpha-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 alpha-TTP can be modified by substances causing oxidative reactions. The human choriocarcinoma cell line BeWo was, therefore, treated with two known pro-oxidants. alpha-TTP expression was determined with immunocytochemistry and evaluated by applying a semiquantitative score. The presence of pro-oxidants in BeWo cells induced alpha-TTP expression. We thus hypothesize that stimulation of alpha-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 Alpha-Tocopherol. This process could occur both in normal pregnancies, as well as in pregnancy disorders presented with intensified 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 Alpha-Tocopherol in pregnancy physiology and pathophysiology.
Vihas T. Vasu - One of the best experts on this subject based on the ideXlab platform.
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Modulation of ozone-sensitive genes in Alpha-Tocopherol Transfer Protein null mice.
Inhalation Toxicology, 2009Co-Authors: Vihas T. Vasu, Brad A. Hobson, Carroll E. Cross, Maret G Traber, Saji Oommen, Giuseppe Valacchi, Jason P. Eiserich, Scott W. Leonard, Kishorchandra GohilAbstract:Alpha-Tocopherol Transfer Protein (ATTP) null mice (ATTP−/−) have a systemic Alpha-Tocopherol (AT) deficiency, with their lung AT levels being
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Genome-Wide Screening of Alpha-Tocopherol Sensitive Genes in Heart Tissue from Alpha-Tocopherol Transfer Protein Null Mice (ATTP−/−)
FEBS Letters, 2007Co-Authors: Vihas T. Vasu, Brad A. Hobson, Kishorchandra Gohil, Carroll E. CrossAbstract:Abstract Alpha-Tocopherol Transfer Protein (ATTP) null mice (ATTP−/−) have a systemic deficiency of Alpha-Tocopherol (AT). The heart AT levels of ATTP−/− are
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Genome‐wide screening of alpha‐tocopherol sensitive genes in heart tissue from alpha‐tocopherol Transfer Protein null mice (ATTP−/−)
FEBS Letters, 2007Co-Authors: Vihas T. Vasu, Brad A. Hobson, Kishorchandra Gohil, Carroll E. CrossAbstract:Alpha tocopherol Transfer Protein (ATTP) null mice (ATTP−/−) have a systemic deficiency of Alpha-Tocopherol (AT). The heart AT levels of ATTP−/− are
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Vitamin E Modulates Inflammatory Responses Induced by Cigarette Smoke (CS) Exposure in alpha -Tocopherol Transfer Protein (TTP) Null Mice
The FASEB Journal, 2006Co-Authors: Vihas T. Vasu, Kishorchandra Gohil, Maret G Traber, Giuseppe Valacchi, Scott W. Leonard, Hnin Hnin Aung, Carroll E. CrossAbstract:CS induced pulmonary inflammatory responses have been reported to be associated with oxidative stress and decreased levels of vitamin E (Alpha-Tocopherol, a-T), possibly due to increased utilizatio...