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Role of GCN2 in guiding the cellular and molecular response to asparaginase in the pancreas

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TitleInfo
Title
Role of GCN2 in guiding the cellular and molecular response to asparaginase in the pancreas
Name (type = personal)
NamePart (type = family)
Phillipson-Weiner
NamePart (type = given)
Lindsey
NamePart (type = date)
1989-
DisplayForm
Lindsey Phillipson-Weiner
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Anthony
NamePart (type = given)
Tracy G
DisplayForm
Tracy G Anthony
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Watford
NamePart (type = given)
Malcolm
DisplayForm
Malcolm Watford
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
McAuliffe
NamePart (type = given)
Geoffrey
DisplayForm
Geoffrey McAuliffe
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 (encoding = w3cdtf); (qualifier = exact)
2015
DateOther (qualifier = exact); (type = degree)
2015-10
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2015
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
Asparaginase is a chemotherapy agent used in the treatment of acute lymphoblastic leukemia. Asparaginase can cause severe pancreatitis but the molecular basis is unknown. In liver of mice, the eIF2 kinase GCN2 is essential for mitigating metabolic stress caused by asparaginase. This study examined the role of GCN2 in the pancreas of mice treated with asparaginase. Eight week old wild type or GCN2 KO mice were injected once daily for 8 d with either 3 IU/g BW of saline or asparaginase. Eight hours after final injection, mice were sacrificed and pancreata were weighed and harvested. In GCN2 KO mice treated with asparaginase, pancreas weights were significantly increased (P<0.05) and the organs visibly enlarged. Histological examination revealed ductal dilatation and swollen acinar cells in GCN2 KO only. Oil red O staining and measurement of pancreas triglycerides ruled out lipid accumulation as a contributing factor. No signs of cell death by TUNEL stain were detected in the pancreas, and serum amylase activity did not differ among treatment groups. However, Pancreatitis Associated Protein (PAP) mRNA expression was elevated in livers of asparaginase-treated GCN2 KO mice only. Phosphorylation of eIF2 and pancreatic expression of asparagine synthetase were similar among treatment groups, but mTORC1 signaling was decreased to the greatest extent in the pancreata of asparaginase-treated GCN2 KO mice. Additionally, transmission electron microscopy revealed evidence of ER stress in GCN2 KO mice treated with asparaginase. These data suggest that loss of GCN2 predisposes the pancreas toward the development of asparaginase-associated pancreatitis. NIH HD070487
Subject (authority = RUETD)
Topic
Nutritional Sciences
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_6713
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (xiii, 78 p. : ill.)
Note (type = degree)
M.S.
Note (type = bibliography)
Includes bibliographical references
Subject (authority = ETD-LCSH)
Topic
Asparaginase
Subject (authority = ETD-LCSH)
Topic
Pancreatitis
Note (type = statement of responsibility)
by Lindsey Phillipson-Weiner
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/T3M90BNF
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
Phillipson-Weiner
GivenName
Lindsey
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2015-09-08 11:54:07
AssociatedEntity
Name
Lindsey Phillipson-Weiner
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)
2015-10-31
DateTime (encoding = w3cdtf); (qualifier = exact); (point = end)
2017-10-30
Type
Embargo
Detail
Access to this PDF has been restricted at the author's request. It will be publicly available after October 30th, 2017.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
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Technical

RULTechMD (ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
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