TitleJun N-terminal kinase 1 (JNK1) as a molecular target to limit cellular mortality under hypoxia
NameBetigeri, Seema S. (Seema Shreesh) (author), Minko, Tamara (chair), Michniak, Bozena (internal member), You, Guofeng (internal member), Mirochnitchenko, Oleg (outside member), Rutgers University, Graduate School - New Brunswick,
DescriptionMany 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.
NoteIncludes bibliographical references (p. 138-153)
Noteby Seema S. Betigeri
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
RightsThe author owns the copyright to this work.