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Jun N-terminal kinase 1 (JNK1) as a molecular target to limit cellular mortality under hypoxia
Descriptive
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Text
TitleInfo
(ID = T-1)
Title
Jun N-terminal kinase 1 (JNK1) as a molecular target to limit cellular mortality under hypoxia
Identifier
ETD_1389
Identifier
(type = hdl)
http://hdl.rutgers.edu/1782.2/rucore10001600001.ETD.000050494
Language
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eng
Genre
(authority = marcgt)
theses
Subject
(ID = SBJ-1);
(authority = RUETD)
Topic
Pharmaceutical Science
Subject
(ID = SBJ-1);
(authority = ETD-LCSH)
Topic
Protein kinases
Subject
(ID = SBJ-1);
(authority = ETD-LCSH)
Topic
Cell death
Abstract
Many pathological conditions and environmental impacts lead to a decrease in tissue oxygen supply and severe cellular hypoxia. This secondary hypoxia can disturb cellular homeostasis, limiting the efficacy of the prescribed treatment for the primary disease, eventually leading to cellular and organismal death. Jun N-terminal kinase 1 (JNK1) plays a central role in the development of cellular damage under hypoxia, hypoxia/reoxygenation and ischemia/reperfusion conditions. Therefore, we selected JNK1 protein as a molecular target to limit cellular damage and death during hypoxia. The primary objective of this research was to study the influence of the suppression of JNK1 on the development of cellular hypoxic damage. It was hypothesized that suppression of JNK1 will decrease cellular mortality under hypoxia and may increase the efficacy of traditional treatment of many pathological conditions. The hypothesis was verified under both in vitro and in vivo conditions. Another objective was to develop a non-viral system for intracellular delivery of antisense oligonucleotides (ASO) and small interfering RNA (siRNA). ASO and siRNA targeted to JNK1 mRNA delivered by neutral and cationic liposomes, respectively, showed high efficiency in suppressing JNK1 protein. Such suppression limited the caspase dependent apoptosis signaling pathway and decreased cellular mortality induced by severe hypoxia. The results suggest that JNK1 protein might be an attractive target for antihypoxic therapy to increase resistance to many pathological conditions and diseases accompanied by cellular hypoxia.
PhysicalDescription
Extent
xv, 155 p. : ill.
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application/pdf
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text/xml
Note
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Ph.D.
Note
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Includes bibliographical references (p. 138-153)
Note
(type = statement of responsibility)
by Seema S. Betigeri
Name
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Betigeri
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Seema S. (Seema Shreesh)
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1975
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author
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Seema S. Betigeri
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Minko
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Tamara
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chair
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Advisory Committee
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Tamara Minko
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(ID = NAME-3);
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(type = family)
Michniak
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(type = given)
Bozena
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internal member
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Advisory Committee
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Bozena Michniak
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(type = family)
You
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(type = given)
Guofeng
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internal member
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Advisory Committee
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Guofeng You
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(ID = NAME-5);
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NamePart
(type = family)
Mirochnitchenko
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Oleg
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outside member
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Advisory Committee
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Oleg Mirochnitchenko
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NamePart
Rutgers University
Role
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degree grantor
Name
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Graduate School - New Brunswick
Role
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school
OriginInfo
DateCreated
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(qualifier = exact)
2009
DateOther
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(type = degree)
2009-01
Place
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xx
Location
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NjNbRU
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TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier
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ETD
RelatedItem
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TitleInfo
Title
Graduate School - New Brunswick Electronic Theses and Dissertations
Identifier
(type = local)
rucore19991600001
Identifier
(type = doi)
doi:10.7282/T3GM87MN
Genre
(authority = ExL-Esploro)
ETD doctoral
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Rights
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The author owns the copyright to this work.
Copyright
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Copyright protected
Availability
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Open
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Detail
Non-exclusive ETD license
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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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5550080
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