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Regulation of drug transporters
Descriptive
TitleInfo
Title
Regulation of drug transporters
Name
(type = personal)
NamePart
(type = family)
Zhang
NamePart
(type = given)
Qiang
NamePart
(type = date)
1978-
DisplayForm
Qiang Zhang
Role
RoleTerm
(authority = RULIB)
author
Name
(type = personal)
NamePart
(type = family)
You
NamePart
(type = given)
Guofeng
DisplayForm
Guofeng You
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
chair
Name
(type = personal)
NamePart
(type = family)
Minko
NamePart
(type = given)
Tamara
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Tamara Minko
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Michniak-Kohn
NamePart
(type = given)
Bozena
DisplayForm
Bozena Michniak-Kohn
Affiliation
Advisory Committee
Role
RoleTerm
(authority = RULIB)
internal member
Name
(type = personal)
NamePart
(type = family)
Pan
NamePart
(type = given)
Zui
DisplayForm
Zui Pan
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)
2012
DateOther
(qualifier = exact);
(type = degree)
2012-05
CopyrightDate
(qualifier = exact)
2012
Place
PlaceTerm
(type = code)
xx
Language
LanguageTerm
(authority = ISO639-2b);
(type = code)
eng
Abstract
(type = abstract)
Organic anion transporters (OATs) are of great importance in the body disposition of a variety of clinical drugs, including anti-cancer, anti-HIV, antibiotics and anti-inflammatory drugs. Long-term regulations of OATs are mainly mediated by gene expression, and short-term regulations are mainly post-translational modifications such as phosphorylation and glycosylation. In the present study, we investigate the constitutive and PKC-regulated trafficking of both hOAT1 and hOAT4 in COS-7 cells. We observed that the internalization of both transporters was accelerated by PKC activation in COS-7 cells. However, the recycling rate of hOAT1 was not affected by PMA treatment. Using approaches of pharmacology and molecular biology, hOAT1 and hOAT4 transporters have been demonstrated to internalize partly via a dynamin- and clathrin-dependent pathway. We observed that overexpression of NHERF1 significantly delayed the internalization of hOAT4 and this observation suggests that the interaction between the PDZ-binding motif of hOAT4 and NHERF1 is involved in the regulation of hOAT4 trafficking by NHERF1. The simultaneous mutations of both leucine residues (L6A/L7A) of hOAT1 resulted in a complete loss of function and the compete loss of function of L6A/L7A hOAT1 was due to the absence of mature form of this mutant at the cell surface and in total cellular extract. It seems that the L6L7 motif does not play a role in the hOAT1 trafficking from the cell surface, and may be involved in its stability. Ubiquitination of membrane proteins has been shown to regulate internalization, postinternalization sorting and degradation of other membrane proteins. Our current investigation focuses on the internalization and degradation of OATs transporters. The major discoveries from our current study are 1) activation of PKC promotes OAT1 ubiquitination both in vitro and in vivo. 2) OAT1 ubiquitination mainly occurs through K48-linked polyubiquitin chains. 3) K48-linked polyubiquitination plays an essential role in PKC-regulated internalization and degradation of OAT1.
Subject
(authority = RUETD)
Topic
Pharmaceutical Science
RelatedItem
(type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
Identifier
ETD_3900
PhysicalDescription
Form
(authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
xiv, 161 p. : ill.
Note
(type = degree)
Ph.D.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = vita)
Includes vita
Note
(type = statement of responsibility)
by Qiang Zhang
Subject
(authority = ETD-LCSH)
Topic
Anions
Subject
(authority = ETD-LCSH)
Topic
Drug delivery systems
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000065308
RelatedItem
(type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
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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/T3XW4HQK
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
Zhang
GivenName
Qiang
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = start)
2012-04-10 21:30:33
AssociatedEntity
Name
Qiang Zhang
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)
2012-05-31
DateTime
(encoding = w3cdtf);
(qualifier = exact);
(point = end)
2012-11-30
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after November 30th, 2012.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical
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2701824
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