Life Sciences Commons^™

Synaptotagmin C2b Ca2+-Binding Loops Impose Distinct Exocytosis Phenotypes, Michael W. Schmidtke

Wayne State University Theses

Regulated exocytosis from chromaffin cells in the adrenal medulla plays a critical role in maintaining organismal homeostasis. In the absence of stress, these cells release physiologically relevant substances into the blood stream only in limited quantities, whereas stressful conditions result in a rapid deluge of signaling molecules used, for example, to increase heart rate and pain tolerance. Although the cellular mechanisms governing the switch from low-level to stress-induced secretion are not well understood, recent evidence has implicated the exocytotic Ca2+-sensing protein Synaptotagmin (Syt) in this role.

Two isoforms of Syt are expressed in chromaffin cells (Syt-1 and Syt-7), and each …

The Nh2-Hypervariable Region Modulates The Binding Affinity Of Troponin T For Tropomyosin, Chinthaka Kaushalya Amarasinghe

Wayne State University Theses

The troponin complex plays a central role in the allosteric function of sarcomeric thin filaments by enacting conformational changes during the Ca2+-regulated contraction and relaxation of striated muscle. The troponin subunit T (TnT) has two binding sites for tropomyosin (Tm) and is responsible for anchoring the troponin complex to the thin filament. Although the C-terminal and middle regions of the TnT polypeptide chain are highly conserved among the three muscle type isoforms, the hypervariable N-terminal region has evolutionarily diverged significantly among isoforms. Previous studies have shown that the N-terminal variable region fine-tunes Ca2+ regulation of muscle contractility via modulation of …

Mrna Granules And Ischemic Preconditioning, Michelle Rei Smith

Wayne State University Theses

Brain ischemia and reperfusion that occurs after stroke and cardiac arrest, causes translation arrest (TA) in neurons which is irreversible in neurons that will undergo delayed neuronal death. TA is linked to mRNA granules, which are involved in ischemia-induced stress genes translation. Ischemic preconditioning (IPC) is the most protective response known that protects neurons from a lethal ischemic insult. In this thesis I studied the effects of (1) sublethal durations of ischemia, (2) IPC and (3) cycloheximide (CHX) on the formation of mRNA granules at 1 hour of reperfusion and the colocalization of HuR in the mRNA granules. All durations …

Effect Of Exogenous Leptin On Thrombotic And Metabolic Profiles Of Fvb/B6 Lipodystrophic Mice, Hoda Chaouki Kadouh

Wayne State University Theses

Lipodystrophy caused by fat deficiency contributes to metabolic disease for which several treatment modalities have been implemented, with leptin therapy being the most effective to date. In addition to playing a role in energy homeostasis and metabolism, leptin was also shown to play a pro-thrombotic role in mice. This role was not examined in fatless mice, neither was thrombosis measured. The AZIP/F-1 (FVB) lipodystrophic mouse appeared to have a prolonged arterial occlusion time (p〈0.05) in a trial done in our lab, with clotting factors being normal. The present study was designed to observe the thrombotic and metabolic characteristics of fatless …