The Biophysical Alterations To Pulmonary Surfactant During Lung Injury, Scott D. Milos

Electronic Thesis and Dissertation Repository

Pulmonary surfactant is a lipoprotein mixture responsible for reducing surface tension of the lung. In this thesis, we investigate the impact of lung injury on surfactant composition and function, with a specific focus on cholesterol content. First, the impact of a high cholesterol diet on surfactant function was assessed in three models of lung injury. It was hypothesized that serum hypercholesterolemia would increase host susceptibility to surfactant functional impairments. Secondly, the impact of injurious ventilation on intracellular surfactant within the lung was investigated. It was hypothesized injurious ventilation would produce alterations to lamellar body surfactant. Overall, the data suggest that …

Regulation Of The High-Affinity Choline Transporter Activity And Trafficking In Alzheimer’S Disease-Related Pathological Conditions, Leah K. Cuddy

Electronic Thesis and Dissertation Repository

Cholinergic neurons play a key role in cognitive processes through the action of the neurotransmitter acetylcholine (ACh). Dysfunction of these neurons occurs in several neurodegenerative disorders, including Alzheimer’s disease (AD). The high-affinity choline transporter CHT recycles choline back into synaptic terminals, which is the rate-limiting step to ACh production. CHT proteins traffic between the cell surface and subcellular organelles in a constitutive manner, which maintains plasma membrane transporter levels, thereby regulating CHT activity and maintaining cholinergic transmission. Pathological conditions associated with AD may alter CHT function in a manner that reduces choline uptake activity and impairs cholinergic neurotransmission. Thus, my …

Cholesterol-Mediated Dysfunction Of Surfactant Effects Of Surfactant Protein-A And Diet-Induced Hypercholesterolemia, Joshua Qua Hiansen

Electronic Thesis and Dissertation Repository

This thesis explored the effects of cholesterol and SP-A on surfactant function in vitro, and lung function in vivo. In the first experiment, we determined whether SP-A could mitigate cholesterol-mediated surfactant dysfunction. We hypothesized that SP-A can mitigate the surfactant inhibition caused by high cholesterol. In the second experiment, we tested the contribution of diet-induced serum hypercholesterolemia to surfactant composition and the development of lung injury in rats. We hypothesized that serum hypercholesterolemia would increase the amount of cholesterol in surfactant and would cause rats to develop more severe lung injury. Our results indicate that SP-A mitigates cholesterol-mediated surfactant …