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The Role Of The Intermembrane Domain Of Mulan In Mitophagy And Cell Death, Jared M. Herbert
The Role Of The Intermembrane Domain Of Mulan In Mitophagy And Cell Death, Jared M. Herbert
Honors Undergraduate Theses
Mulan is an E3 ubiquitin ligase and an E3 SUMO ligase embedded in the outer mitochondrial membrane. Mulan plays a major role in various cell processes including cell growth, mitophagy, apoptosis, and mitochondrial dynamics. In addition, its deregulation is involved in the development and progression of several human disorders such as neurodegeneration and heart disease. There are two main discernible domains in Mulan: a large cytoplasmic domain that encodes the RING-finger motif and carries out the catalytic activity of the protein; the second domain of Mulan is exposed to the intermembrane space of mitochondria, and its function remains unknown. This …
Cerium Oxide Nanoparticles Sensitize Pancreatic Cancer Cells To Radiation By Promoting Acidic Ph, Ros, And Jnk Dependent Apoptosis, Melissa Wason
Cerium Oxide Nanoparticles Sensitize Pancreatic Cancer Cells To Radiation By Promoting Acidic Ph, Ros, And Jnk Dependent Apoptosis, Melissa Wason
Electronic Theses and Dissertations
Side effects of radiation therapy (RT) remain the most challenging issue for pancreatic cancer treatment. In this report we determined whether and how cerium oxide nanoparticles (CONPs) sensitize pancreatic cancer cells to RT. CONP pretreatment enhanced radiation-induced reactive oxygen species (ROS) production preferentially in acidic cell-free solutions as well as acidic human pancreatic cancer cells. In acidic environments, CONPs favor the scavenging of superoxide radical over the hydroxyl peroxide resulting in accumulation of the latter whereas in neutral pH CONPs scavenge both. CONP treatment prior to RT markedly potentiated the cancer cell apoptosis both in culture and in tumors and …
The Role Of Mitochondrial Omi/Htra2 Protease In Protein Quality Control And Mitophagy, Camilla Ambivero
The Role Of Mitochondrial Omi/Htra2 Protease In Protein Quality Control And Mitophagy, Camilla Ambivero
Electronic Theses and Dissertations
Omi/HtrA2 is a mitochondrial serine protease with a dual and opposite function depending on its subcellular localization. Most of the previous studies focused on Omi/HtrA2’s pro-apoptotic function when the protein is released to the cytoplasm. It is becoming apparent that the main function of Omi/HtrA2 is within the mitochondria, where it has a pro-survival role. However, its mechanism is still poorly understood. To this end, we used the yeast two-hybrid system to dissect the Omi/HtrA2 pathway by identifying novel interactors and substrates. Our studies revealed a novel function of Omi/HtrA2 in the regulation of a deubiquitinating (DUB) complex. In addition …
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 …
Biophysical Characterization Of The Membrane Binding Domain Of The Pro-Apoptotic Protein Bax, Pranav Garg
Biophysical Characterization Of The Membrane Binding Domain Of The Pro-Apoptotic Protein Bax, Pranav Garg
Electronic Theses and Dissertations
The BCL-2 family of proteins tightly regulates the delicate balance between life and death. The pore forming Bax is a pro-apoptotic member belonging to this protein family. At the onset of apoptosis, monomeric cytoplasmic Bax translocates to the outer mitochondrial membrane, forms oligomeric pores thereby letting mitochondrial cytochrome c enter the cytosol and initiate the apoptotic cascade. The C-terminal "helix 9" is thought to mediate the membrane binding of BAX. A 20-amino acid peptide corresponding to Bax C-terminus (VTIFVAGVLTASLTIWKKMG) and two mutants where the two lysines are replaced with Glu (charge reversal mutant, EE) or Leu (charge neutralization mutant, LL) …
The Sheddase Activity Of Adam10/Adam17 On Cxcl16 Increases Proliferation And Survival Of Colorectal Cancer Cells, Tamu C. Talton
The Sheddase Activity Of Adam10/Adam17 On Cxcl16 Increases Proliferation And Survival Of Colorectal Cancer Cells, Tamu C. Talton
Electronic Theses and Dissertations
CXCL16 is an interferon-inducible chemokine of the CXC-subfamily and functions as an adhesion molecule, when membrane bound, and a chemoattractant when soluble. Upregulation of cell associated CXCL16 (cCXCL16) in colorectal cancer is associated with increased tumor infiltrating lymphocytes and good prognosis. ADAM10 and ADAM17 are metalloproteinases responsible for cleaving CXCL16, releasing soluble CXCL16 (sCXCL16) and contributing to proliferation and migration of mesangial cells, in kidney inflammatory disease. We hypothesize that cCXCL16 is a substrate for ADAM10 and ADAM17 cleavage in colorectal cancer, releasing sCXCL16, which mediates cell proliferation. To this end, we first identified CXCL16 in the human colon carcinoma …