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Molecular mechanisms of cytotoxicity induced by ribosome-inactivating proteins in mammalian cells
Descriptive
TypeOfResource
Text
TitleInfo
(ID = T-1)
Title
Molecular mechanisms of cytotoxicity induced by ribosome-inactivating proteins in mammalian cells
Identifier
ETD_2901
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.1/rucore10001600001.ETD.000056279
Language
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(authority = ISO639-2);
(type = code)
eng
Genre
(authority = marcgt)
theses
Subject
(ID = SBJ-1);
(authority = RUETD)
Topic
Animal Sciences
Subject
(ID = SBJ-2);
(authority = ETD-LCSH)
Topic
Ribosomes
Subject
(ID = SBJ-3);
(authority = ETD-LCSH)
Topic
Cell-mediated cytotoxicity
Subject
(ID = SBJ-4);
(authority = ETD-LCSH)
Topic
Ricin
Subject
(ID = SBJ-5);
(authority = ETD-LCSH)
Topic
Apoptosis
Subject
(ID = SBJ-6);
(authority = ETD-LCSH)
Topic
Verocytotoxins
Abstract
(type = abstract)
Ribosome-inactivating proteins (RIP) represent a family of plant and bacterial toxins that inhibit protein synthesis and are cytotoxic to mammalian cells. Ricin is isolated from seeds of the castor bean plant and has potential as a weapon of bioterrorism. Shiga-like toxins (stx) are produced from enterohemorrahagic Escherichia coli strains, and contamination of food by stx represents a substantial public health threat. Both ricin and stx consist of A and B chains. The A-chain of each protein inactivates the ribosome by cleaving an adenine from the ribosomal RNA. The B-chain of ricin (RTB) binds to galactose binding sites on the cell surface while the pentameric B subunit of stx binds to the cell surface receptor, globotriaosylceramide to facilitate cell entry. While both ricin and stx inhibit protein synthesis and induce cell death, the molecular mechanisms that underlie these effects are relatively unexplored. An ultimate goal of this research is to produce recombinant mutant ricin A-chain (RTA) proteins to study the role of protein synthesis inhibition in ricin-induced cytotoxicity. Therefore, we were interested in establishing a mammalian cell culture model that was sensitive to RTA alone. The cell line MAC-T, an immortalized, nontransformed epithelial cell line, was more sensitive than Vero cells and HeLa cells in terms of the time it took to induce caspase-3/7 activation. While ricin induced higher caspase-3/7 activity than RTA at lower concentrations (0.1 to 10 ng/ml), similar caspase activation was observed at concentrations of 0.1 µg/ml with either protein. Ribosome depurination, protein synthesis inhibition, and apoptosis were observed in MAC-T cells treated with RTA alone. RTA alone also induced JNK and p38 MAP kinase activation in a time- and concentration-dependent manner that preceded apoptosis. Inhibition of the JNK pathway by chemical inhibitors or small interfering RNA reduced RTA-induced apoptosis. In contrast, inhibition of the p38 MAP kinase pathway had little effect on RTA-induced apoptosis. In summary, the major findings of this research are the establishment of the MAC-T cell line as a sensitive cell culture model for future study of ricin and the finding that the JNK pathway plays a major role in RTA-induced cytotoxicity.
PhysicalDescription
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electronic resource
Extent
xii, 77 p. : ill.
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application/pdf
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text/xml
Note
(type = degree)
M.S.
Note
(type = bibliography)
Includes bibliographical references
Note
(type = statement of responsibility)
by Ju-Shun Cheng
Name
(ID = NAME-1);
(type = personal)
NamePart
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Cheng
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(type = given)
Ju-Shun
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1978-
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author
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Ju-Shun Cheng
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Cohick
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(type = given)
Wendie S
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chair
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Advisory Committee
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Wendie S Cohick
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(type = personal)
NamePart
(type = family)
Bagnell
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(type = given)
Carol
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internal member
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Advisory Committee
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Carol Bagnell
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(ID = NAME-4);
(type = personal)
NamePart
(type = family)
Watford
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(type = given)
Malcolm
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internal member
Affiliation
Advisory Committee
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Malcolm Watford
Name
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NamePart
Rutgers University
Role
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degree grantor
Name
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NamePart
Graduate School - New Brunswick
Role
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(authority = RULIB)
school
OriginInfo
DateCreated
(qualifier = exact)
2010
DateOther
(qualifier = exact);
(type = degree)
2010-10
Place
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(type = code)
xx
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
(type = RULIB)
ETD
RelatedItem
(type = host)
TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
(type = local)
rucore19991600001
Location
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(displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier
(type = doi)
doi:10.7282/T3028RBD
Genre
(authority = ExL-Esploro)
ETD graduate
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Rights
RightsDeclaration
(AUTHORITY = GS);
(ID = rulibRdec0006)
The author owns the copyright to this work.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
RightsHolder
(ID = PRH-1);
(type = personal)
Name
FamilyName
Cheng
GivenName
Ju-Shun
Role
Copyright Holder
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Type
Permission or license
DateTime
2010-09-24 15:21:37
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Role
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Name
Ju-Shun Cheng
Affiliation
Rutgers University. Graduate School - New Brunswick
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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.
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Technical
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ETD
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application/pdf
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application/x-tar
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2109440
Checksum
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