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Full-Text Articles in Molecular Biology
Signals Delivered By Interleukin-7 Regulate The Activities Of Bim And Jund In T Lymphocytes, Shannon Moore Ruppert
Signals Delivered By Interleukin-7 Regulate The Activities Of Bim And Jund In T Lymphocytes, Shannon Moore Ruppert
Electronic Theses and Dissertations
Interleukin-7 (IL-7) is an essential cytokine for lymphocyte growth that has the potential for promoting proliferation and survival. While the survival and proliferative functions of IL-7 are well established, the identities of IL-7 signaling components in pathways other than JAK/STAT, that accomplish these tasks remain poorly defined. To this end, we used IL-7 dependent T-cells to examine those components necessary for cell growth and survival. Our studies revealed two novel signal transducers of the IL-7 growth signal: BimL and JunD. IL-7 promoted the activity of JNK (Jun N-terminal Kinase), and that JNK, in turn, drove the expression of JunD, a …
The Dynamic Functions Of Bax Are Dependent On Key Structural And Regulatory Features, Rebecca Boohaker
The Dynamic Functions Of Bax Are Dependent On Key Structural And Regulatory Features, Rebecca Boohaker
Electronic Theses and Dissertations
Bax is an essential mediator of cell fate. Since its discovery in 1985 as a protein that interacts with the anti-apoptotic protein, Bcl-2, key elements related to its function, structure and regulation remains to be determined. To this end, mitochondrial metabolism was examined in non-apoptotic Bax-deficient HCT-116 cells as well as primary hepatocytes from Bax-deficient mice. Although mitochondrial density and mitochondrial DNA content was the same in Bax-containing and Bax -deficient cells, MitoTracker staining patterns differed, suggesting the existence of Bax -dependent functional differences in mitochondrial physiology. Oxygen consumption and cellular ATP levels were reduced in Bax -deficient cells, while …
Transplantation Of Pluripotent Stem Cells Confers Cardiac Protection In Dox-Induced Heart Failure Through Notch-1 Pathway, Hilda Merino-Chavez
Transplantation Of Pluripotent Stem Cells Confers Cardiac Protection In Dox-Induced Heart Failure Through Notch-1 Pathway, Hilda Merino-Chavez
Electronic Theses and Dissertations
Doxorubicin (DOX) is the antineoplastic drug of preference used to treat a wide variety of malignancies, with high survival rates among treated patients. However, the benefits of this drug have become less appealing due to the side effects that occur such as DOX-induced cardiomyopathy (DIC) and an increased risk of myocardial infarction (MI). Therefore, there is an urgent need to explore the therapeutic options to treat DIC. In this context, adult stem cells have been used as a source to reduce cardiomyocyte apoptosis in DIC; however, the effects of transplanted embryonic stem (ES) cells and induced pluripotent stem (iPS) cells …
Hdm2 Small-Molecule Inhibitors For Therapeutic Intervention In B-Cell Lymphoma, Angela Sosin
Hdm2 Small-Molecule Inhibitors For Therapeutic Intervention In B-Cell Lymphoma, Angela Sosin
Wayne State University Dissertations
Lymphomas frequently retain wild-type (wt) p53 function but overexpress HDM2, compromising p53 activity. Therefore, lymphoma is a suitable model for studying therapeutic value of disrupting HDM2-p53 association by small-molecule inhibitors (SMIs). HDM2 SMIs have been developed and are currently under various stages of preclinical and clinical investigation. This study examined various molecular mechanisms associated and biological effects of two different classes of HDM2 SMIs: the spiro-oxindoles (MI-219) and cis-imidazoline (Nutlin-3) in lymphoma cell lines and patient-derived B-lymphoma cells. Surprisingly, results revealed significant quantitative and qualitative differences between these two agents. At the molecular level, effect of Nutlin-3 was generally more …