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The role of beta-carotene and its cleavage enzymes during vitamin A deficiency and mammalian embryonic development

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TitleInfo
Title
The role of beta-carotene and its cleavage enzymes during vitamin A deficiency and mammalian embryonic development
Name (type = personal)
NamePart (type = family)
Spiegler
NamePart (type = given)
Elizabeth Kuhn
NamePart (type = date)
1986-
DisplayForm
Elizabeth Spiegler
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Quadro
NamePart (type = given)
Loredana
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Loredana Quadro
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Brasaemle
NamePart (type = given)
Dawn
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Dawn Brasaemle
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Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Breslin
NamePart (type = given)
Paul
DisplayForm
Paul Breslin
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Storch
NamePart (type = given)
Judith
DisplayForm
Judith Storch
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Sarkar
NamePart (type = given)
Dipak
DisplayForm
Dipak Sarkar
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = personal)
NamePart (type = family)
Hammerling
NamePart (type = given)
Ulrich
DisplayForm
Ulrich Hammerling
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - New Brunswick
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2014
DateOther (qualifier = exact); (type = degree)
2014-05
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Vitamin A deficiency during pregnancy is a widespread health problem, which can detrimentally affect embryonic development. Since most of the world has limited access to preformed vitamin A (retinoids), it is important to understand whether the more abundant dietary precursor to vitamin A (beta-carotene, bC) can adequately support embryonic development. bC is converted to vitamin A by its cleavage enzymes: the symmetric cleavage enzyme beta-carotene 15,15’-oxygenase (CMO1) which generates retinaldehyde, and the asymmetric cleavage enzyme beta-carotene 9’,10’-oxygenase (CMO2), which generates beta-apo-10’-carotenal. Both enzymes are expressed in mammalian embryos throughout development. We studied bC metabolism in a mouse model of severe vitamin A deficiency – the Lrat-/-Rbp-/- mice, which cannot store retinol via lecithin:retinol acyltransferase (LRAT) or mobilize retinol from the liver via retinol-binding protein (RBP), and therefore produce highly malformed embryos when deprived of dietary vitamin A. We found that bC supplementation during a critical window of organ development rescued ~40% of Lrat-/-Rbp-/- embryos from symptoms of vitamin A deficiency, while supplementation after organ development did not improve the embryonic phenotype. This study indicated that bC is a good source of retinoids during pregnancy, but cannot fully support embryonic development even after prolonged administration. We gained further insight into the ability to rescue embryos from vitamin A deficiency by studying Cmo1-/-Rbp-/- mice and our novel Cmo1-/-Rbp-/-Cmo2-/- strain. We found that spontaneous bC oxidation, rather than CMO2 activity, could generate small amounts of retinoids to improve the embryonic phenotype in the absence of CMO1. On the other hand, CMO2 deficiency on a background of vitamin A deficiency (Cmo2-/-Rbp-/- mice) caused a severe embryonic phenotype that could not be rescued by bC despite the potential to generate retinaldehyde via CMO1. Cmo2-/-Rbp-/- embryos were rescued following maternal supplementation with beta-apo-10’-carotenal, the apocarotenoid normally generated from bC by CMO2 action, which also can be converted to retinoids by CMO1. We found that beta-apo-10’-carotenal may influence mitochondrial energy homeostasis through a PKC signaling complex. Overall, these studies showed that beta-apo-10’-carotenal may be more effective than bC in supporting embryogenesis, and suggest that this apocarotenoid should be a recommended component of the human diet.
Subject (authority = RUETD)
Topic
Nutritional Sciences
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_5384
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xviii, 210 p. : ill.
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Elizabeth Kuhn Spiegler
Subject (authority = ETD-LCSH)
Topic
Beta carotene
Subject (authority = ETD-LCSH)
Topic
Vitamin A deficiency
Subject (authority = ETD-LCSH)
Topic
Vitamin A in human nutrition
Subject (authority = ETD-LCSH)
Topic
Embryology, Human
RelatedItem (type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier (type = local)
rucore19991600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3X065CR
Genre (authority = ExL-Esploro)
ETD doctoral
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Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Spiegler
GivenName
Elizabeth
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2014-04-04 15:20:31
AssociatedEntity
Name
Elizabeth Spiegler
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - New Brunswick
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
RightsEvent
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2014-05-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2015-05-31
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after May 31st, 2015.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
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