Biochemistry Commons^™

Steroid-Coa Ligases, Fadd17a1 And Fadd19a1, And Their Role In Cholesterol Side-Chain Degradation In Mycobacterium Tuberculosis, Johnathan Salim Abou-Fadel

Open Access Theses & Dissertations

Mycobacterium tuberculosis (Mtb) is a serious health issue arising from the increasing incidence of multi-drug resistant (MDR-TB) strains that are becoming more prevalent in high-risk countries, especially here in the Texas/Mexico border. Confirmed cases and outbreaks in schools and hospitals are more frequent in this region due to the high-volume pedestrian traffic between the two cities, and the lack of a modernized health system in Mexico. Identification of new Mtb metabolic pathways for development of novel antitubercular drugs is urgently needed. The goal of this current work investigates two Mtb fatty acyl-CoA ligase enzymes' (FadD17A1 and FadD19A1) to explore whether …

Label-Free Quantitative Proteomics Reveals A Novel Sgta/Peroxiredoxin I Complex That Regulates Androgen Receptor Activity, Yenni Alejandra Garcia

Open Access Theses & Dissertations

The dynamic Hsp70-90 chaperone machinery along with its cochaperone partners are well-characterized for their ability to fold, assemble, and regulate steroid hormone receptors (SHRs). Human small glutamine rich tetratricopeptide repeat (TPR) containing protein alpha (SGTA) is a recently identified protein that has a characteristic Hsp90-binding TPR domain and is a key participant in the androgen, glucocorticoid, and progesterone receptor signaling pathway. In addition, SGTA plays a role in cellular processes such as cell cycle progression and apoptosis. We have demonstrated that SGTA binds directly to both Hsp70 (kd = 6 μM) and Hsp90 (kd = 11 μM). In a cell-free …

Characterization Of The Nodamura Virus Rna Dependent Rna Polymerase And Formation Of Rna Replication Complexes In Mammalian Cells, Vincent Ulysses Gant

Open Access Theses & Dissertations

Positive-strand RNA viruses amplify their genomes in membrane-bound structures associated with intracellular membranes and organelles called replication complexes (RCs). Here, we begin to elucidate mechanisms of Nodamura virus (NoV; family Nodaviridae) RC assembly. The literature reports that NoV-infected muscle tissue exhibits mitochondrial aggregation and rearrangement of mitochondrial structure, leading to disorganization of the muscle fibrils. However, the molecular basis for this pathogenesis and the role of mitochondria in NoV infection remained unclear until now. We tested the hypoThesis that NoV establishes RCs in association with mitochondria in cultured mammalian cells at physiological temperature. We used immunofluorescence confocal microscopy and biochemical …

A Comparative Approach To Assessing The Functional And Structural Characteristics Of Human Fkbp52 In The Regulation Of Steroid Hormone Receptor Signaling Pathway, Diondra Crystal Harris

Open Access Theses & Dissertations

The 52 kDa FK506 binding protein (h52) is a key positive regulator of Androgen Receptor (AR) in cellular and animal models and is an attractive target for the treatment of prostate cancer. Human FKBP52 is a known regulatory protein and co-chaperone that has been shown to play an important role in the regulation of the AR signaling pathway, and in the development of the male sexual phenotype. Cellular studies in mammalian and yeast cells reveal that FKBP52 is a positive regulator of AR, glucocorticoid receptor (GR), and progesterone receptor (PR), potentiating receptor-mediated gene expression up to 60-fold in some systems. …

Giardia Lamblia: Regulation Of Cyst Production By Glycosphingolipids, Tavis Lyle Mendez

Open Access Theses & Dissertations

The diplomonad protist, Giardia lamblia, colonizes and replicates in the small intestine of mammals. In humans, Giardia infection (known as giardiasis) can be symptomatic or asymptomatic with the former being associated with fatty stool, abdominal pain, malnutrition, and weight loss. Both cell-mediated and humoral immune responses against Giardia infection are possible, and adaptive responses have been reported to be important for controlling the infection. Non-immune components such as secretory immunoglobulin, intestinal lipids, and bile acids also play significant roles in determining the severity of the infection by Giardia.

Giardia exists in two morphologic forms--trophozoites and cysts--and maintains a simple life …

Identification And Characterization Of Fkbp52-Specific Inhibitors For The Treatment Of Prostate Cancer, Johanny Tonos De Leon

Open Access Theses & Dissertations

Steroid hormone receptors require the ordered assembly of various chaperone and cochaperone proteins in order to reach a functional state. The final stage in the receptor maturation process requires the formation of a mutimeric complex consisting of Hsp90 dimer, p23, and one of several large immunophilins. Studies conducted previously demonstrated that the large immunophilin FKBP52 acts to potentiate glucocorticoid, androgen, and progesterone receptor signaling pathways. The aim of these studies was to identify and characterize FKBP52-specific inhibitors that would not only serve as tools for the pharmacological analysis of FKBP52-receptor interactions, but may also lead to novel drugs with significant …

Ganglioside-Cytokine Interaction In The Induction Of Primary Brain Cell Death, John Charles Gorbet

Open Access Theses & Dissertations

Gangliosides have been implicated in multiple pathologies affecting the central nervous system (CNS) and recent research has implicated them in playing an active role in the pathogenesis of multiple sclerosis. Empirical studies and theoretical considerations have suggested the possibility of interactions between gangliosides, like GD3, and pro-inflammatory cytokines present in the nervous system. This study sought to investigate the possibility that either individual gangliosides acting alone or complexed with other species interact with the known immune response factor TNF&alpha to initiate or facilitate cell death in the CNS. I examined the cellular viability and gene expression in primary brain cell …

Phosphorylation Of The Glycine Transporter 1, Javier Vargas Medrano

Open Access Theses & Dissertations

The extracellular levels of the neurotransmitter glycine in the brain are tightly regulated by the high-affinity glycine transporter 1 (GlyT1) and the clearance of glycine depends on its rate of transport and the levels of cell surface GlyT1. Over the past years, it has been shown that PKC activation diminishes the activity and promoted phosphorylation of several neurotransmitter transporters including the dopamine, serotonin and norepinephrine transporters however, its role is unknown for the glycine transporter. To get insights into the role of PKC activation on GlyT1 regulation, we used three N-terminus GlyT1 isoforms stably expressed in porcine aortic endothelial (PAE) …