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Role of NFkB and Bcl-2 in IGFBP-3 mediated intrinsic apoptosis

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TitleInfo
Title
Role of NFkB and Bcl-2 in IGFBP-3 mediated intrinsic apoptosis
Name (type = personal)
NamePart (type = family)
Hanke
NamePart (type = given)
Jennifer
NamePart (type = date)
1988-
DisplayForm
Jennifer Hanke
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Cohick
NamePart (type = given)
Wendie S
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Wendie S Cohick
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Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Anthony
NamePart (type = given)
Tracy
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Tracy Anthony
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Bello
NamePart (type = given)
Nick
DisplayForm
Nick Bello
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)
2017
DateOther (qualifier = exact); (type = degree)
2017-05
CopyrightDate (encoding = w3cdtf); (qualifier = exact)
2017
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
The overall goal of this work was to investigate the mechanisms by which IGFBP-3 mediates ribotoxin-induced apoptosis in the non-transformed bovine mammary epithelial cell line MAC-T. For this work, the ribotoxins anisomycin (ANS) and deoxynivalenol (DON), which both activate the intrinsic apoptotic pathway, were investigated. Similar to previous results with ANS, DON increased mRNA and protein levels of IGFBP-3 and knockdown of IGFBP-3 with small interfering (si)RNA attenuated DON-induced apoptosis. These results confirm a role for IGFBP-3 as a key player of intrinsic apoptosis associated with the ribotoxic stress response. However, the specific mechanism by which this occurs is largely unknown. The early stages of intrinsic apoptosis are carefully controlled by members of the Bcl-2 family of proteins which is comprised of both pro- and anti-apoptotic members. The overall ratio between these pro- and anti-apoptotic proteins ultimately dictates the sensitivity or resistance of the cell to apoptotic stimuli. To investigate a role for Bcl-2 proteins, MAC-T cells transfected with IGFBP-3 or control siRNA were treated with ANS or DON and cell lysates were analyzed for changes in expression of Bcl-2 family proteins. IGFBP-3 knockdown significantly increased protein and mRNA levels of the pro-survival protein Bcl-2. Since knockdown of IGFBP-3 did not affect the levels of pro-apoptotic proteins Bax and Bak, the increase in Bcl-2 increased the ratio towards one that favors survival. Given the relationship between Bcl-2 and the NFκB pathway, IGFBP-3 knockdown cells were treated with or without the NFΚB inhibitor phenethyl caffeate (PC). Inhibition of NFκB with PC decreased Bcl-2 protein expression; however, this decrease was also observed in IGFBP-3 knockdown cells in the presence of PC. These data suggest that IGFBP-3 affects Bcl-2 expression through a mechanism that is upstream of NFκB. Interestingly, treatment with PC increased basal expression of IGFBP-3 mRNA and protein, indicating that NFκB represses IGFBP-3 expression in the basal state. In conclusion, IGFBP-3 appears to inhibit expression of Bcl-2 protein. However, while NFκB increases Bcl-2 expression and inhibits IGFBP-3 expression, the mechanisms by which these pathways are linked remain elusive.
Subject (authority = RUETD)
Topic
Endocrinology and Animal Biosciences
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_8016
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (ix, 54 p. : ill.)
Note (type = degree)
M.S.
Note (type = bibliography)
Includes bibliographical references
Subject (authority = ETD-LCSH)
Topic
Insulin-like growth factor-binding proteins
Subject (authority = ETD-LCSH)
Topic
Apoptosis
Note (type = statement of responsibility)
by Jennifer Hanke
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/T3F76GD0
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
Hanke
GivenName
Jennifer
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2017-04-13 15:21:21
AssociatedEntity
Name
Jennifer Hanke
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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Technical

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2017-04-13T15:20:43
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2017-04-13T15:20:43
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