Medical Sciences Commons^™

Er Stress Coupled Pannexin Channel Activation Via Stim Proteins, Ankur Bodalia

Electronic Thesis and Dissertation Repository

Many neurodegenerative diseases, including Alzheimer’s Disease, are associated with ER stress. It is suggested that plasma membrane channels contribute to the increased ionic influx and subsequent cell death in response to ER stress. Pannexin channels, which have been implicated in various pathophysiological conditions, are a suitable candidate for facilitating this response. However, mechanisms of pannexin channel activation are poorly defined. I investigated the potential regulation of pannexin activity by the ER stress sensor, STIM. It was hypothesized that pannexin channel activation during ER stress is contingent on the recruitment of STIM proteins. In neurons, pannexin activation was observed in response …

Pharmacogenetics Of Oral Anticoagulants And Antiplatelets, Inna Gong

Electronic Thesis and Dissertation Repository

Thromboembolic disorders are a major cause of morbidity and mortality. Therapeutic intervention with anticoagulants and antiplatelets greatly reduces the risk of arterial and venous thrombosis. However, the observed large interindividual variation in responsiveness to these drugs indicates that subsets of patients are not attaining optimal therapy, resulting in either lack of antithrombotic effect or elevated bleeding risk. Recently, single nucleotide polymorphisms (SNPs) have been linked to the variation observed in efficacy and toxicity for many cardiovascular drugs.

Warfarin has been the gold standard anticoagulant for prevention of stroke and thromboembolism in atrial fibrillation (AF) and venous thromboembolism (VTE) patients. SNPs …

Fetal And Neonatal Exposure To Nicotine Augments Hepatic Fatty Acid Synthesis In Rat Offspring Long-Term, Noelle L. Ma

Electronic Thesis and Dissertation Repository

While nicotine replacement therapy (NRT) is presumed to be a safer alternative to smoking in pregnancy, the long-term consequences in offspring are still largely unknown. Animal studies now suggest that maternal nicotine exposure during pregnancy and lactation (MNE-PL) leads to a wide variety of adverse outcomes for the offspring, including increased adiposity. The focus of this study was to investigate how MNE-PL in rats may lead to liver dysfunction long-term in offspring through alterations in gene expression and epigenetic modifications. Postnatal day 180 (PND180) offspring exposed to nicotine during pregnancy and lactation (1mg/kg/day) exhibited increased circulating and hepatic triglycerides concomitant …

Characterizing Stomatin-Like Protein 2 And Its Role In Neuron Survival, Lisa A. Foris

Electronic Thesis and Dissertation Repository

Stomatin-like Protein 2 (SLP-2) has been identified as a stress-inducible transcript and has been shown to interact with and stabilize mitochondrial proteins. Since mitochondria are critical for neuronal function, we hypothesized that SLP-2 regulates neuron survival in response to stressful stimuli. A conditional SLP-2 knockout mouse (deletion) and the SN56 cell line (upregulation) were employed to study the role of SLP-2 in mitochondrial dynamics and neuron survival. SLP-2 deficient primary cortical neurons displayed significantly decreased levels of various mitochondrial respiratory chain proteins, indicating SLP-2 contributes to maintenance of mitochondrial membrane integrity. SLP-2 was up-regulated in response to oxidative stress and …