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Characterization of renal transporter expression in mice during pregnancy, lactation, and type I diabetes
Descriptive
TitleInfo
Title
Characterization of renal transporter expression in mice
during pregnancy, lactation, and type I diabetes
during pregnancy, lactation, and type I diabetes
Name
(type = personal)
NamePart
(type = family)
Yacovino
NamePart
(type = given)
Lindsay Lee
NamePart
(type = date)
1986-
DisplayForm
Lindsay Yacovino
Role
RoleTerm
(authority = RULIB)
author
Name
(type = personal)
NamePart
(type = family)
Reuhl
NamePart
(type = given)
Kenneth
DisplayForm
Kenneth Reuhl
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
chair
Name
(type = personal)
NamePart
(type = family)
Aleksunes
NamePart
(type = given)
Lauren
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Lauren Aleksunes
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Gallo
NamePart
(type = given)
Michael
DisplayForm
Michael Gallo
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Thomas
NamePart
(type = given)
Paul
DisplayForm
Paul Thomas
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal 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)
2012
DateOther
(qualifier = exact);
(type = degree)
2012-01
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
Renal transporters regulate the reabsorption and secretion of nutrients, drugs, and toxicants. Modification of their expression and/or activity can alter renal clearance, affecting drug efficacy and toxicity. Prior work has suggested that sex hormones and metabolic changes, like diabetes and obesity, alter renal transporter expression in rodents. The purpose of this thesis was to characterize the mRNA and protein expression of renal uptake and efflux transporters and potential regulatory transcription factors in response to gestation, lactation, and type I diabetes in female C57BL/6 mice. In a time-course study, kidney transporter mRNA and protein expression were evaluated using qPCR, western blot, and immunofluorescence staining on gestation days (GD) 7, 11, 14, and 17 and postnatal days (PD) 1, 15, and 30. Pregnancy caused marked down-regulation of apical efflux transporters Mdr1b, Mrp2, Mrp4, and Mate1 and up-regulation of basolateral efflux transporter Mrp3. Mdr1b and Mrp4 mRNA decreased early in pregnancy and remained low throughout lactation whereas Mrp1, Mrp2, and Mate1 mRNA expression did not begin to decline until mid-gestation. A marked increase in Mrp3 mRNA and protein was observed at mid-gestation. Western blot and immunofluorescence staining confirmed reduced protein expression of Mrp2 and Mrp4 and elevated Mrp3 levels in pregnant mice. For the diabetic pregnancy study, female C57BL/6 mice were treated repeatedly with intraperitoneal doses of vehicle or streptozotocin (STZ) to induce type I diabetes. After two weeks of hyperglycemia, STZ-and vehicle-treated control mice were mated overnight and tissues collected 14 days later. Both efflux and uptake renal transporters were differentially regulated in response to STZ treatment. STZ decreased mRNA expression of Oat2, Oat5, and Mrp3 and elevated levels of Oatp2b1, Oatp4c1, Pept1, Mrp2, Mrp4, and Mrp5. Pregnancy had little effect on STZ-mediated down-regulation of Oat2 and Oat5 mRNA, but did prevent up-regulation of Oatp4c1 and Mrp4 mRNA. In both the time-course and diabetic pregnancy studies, mRNA profiling revealed transcription factors (AhR, PXR, HNF1α, PPARα and Nrf2) that might participate in regulating renal transporter expression. Taken together, these results suggest that renal drug transport and regulatory signaling pathways are altered by endocrine and metabolic changes that occur during pregnancy and diabetes.
Subject
(authority = RUETD)
Topic
Toxicology
RelatedItem
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
Identifier
ETD_3774
PhysicalDescription
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(authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xiv, 158 p. : ill.
Note
(type = degree)
M.S.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = statement of responsibility)
by Lindsay Lee Yacovino
Subject
(authority = ETD-LCSH)
Topic
Renal tubular transport
Subject
(authority = ETD-LCSH)
Topic
Drugs--Effectiveness
Subject
(authority = ETD-LCSH)
Topic
Mice as laboratory animals
Subject
(authority = ETD-LCSH)
Topic
Renal circulation
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000064192
RelatedItem
(type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
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rucore19991600001
Location
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(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier
(type = doi)
doi:10.7282/T3B56HR8
Genre
(authority = ExL-Esploro)
ETD graduate
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Rights
RightsDeclaration
(ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder
(type = personal)
Name
FamilyName
Yacovino
GivenName
Lindsay
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = start)
2012-01-03 19:58:56
AssociatedEntity
Name
Lindsay Yacovino
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.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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2956800
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