Theses and Dissertations from UMD

Permanent URI for this communityhttp://hdl.handle.net/1903/2

New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM

More information is available at Theses and Dissertations at University of Maryland Libraries.

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2010 - 20172

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Subject: search.filters.subject.acid sphingomyelinase

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    Excitation-Contraction Coupling Disruption in a Mouse Model of Niemann-Pick Disease
    (2017) Li, Harry Zichen; Chin, Eva R; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Niemann-Pick disease (NPD) is a lysosomal storage disorder that results from deficient acid sphingomyelinase (ASM) activity. It was recently proposed that ASM and extracellular Ca2+ are required for membrane repair. Since plasma membrane integrity is an important component of excitation-contraction coupling (E-C) and skeletal muscle force production, we hypothesized that there would be E-C coupling defects in NPD related to intracellular calcium (Ca2+) dynamics. Our results demonstrate that ASM deficient (ASM-/-) fibers have a reduced ability to withstand repetitive contractions in comparison to wild-type (WT) fibers, and fibers from ASM-/- mice exhibited lower peak tetanic Ca2+ compared to WT. Lastly, no differences in peak tetanic Ca2+ were found between ASM-/- fibers and WT fibers deprived of Ca2+. Together, these results suggest that both ASM and extracellular Ca2+ are required for optimal E-C coupling in skeletal muscle and for the ability to respond to repetitive contractions that occurs with sustained activity.
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    ROLE OF ACID SPHINGOMYELINASE IN ICAM-1/NHE1-DEPENDENT ENDOCYTOSIS: IMPLICATIONS IN LEUKOCYTE TRANSMIGRATION
    (2010) Serrano, Daniel; Muro, Silvia; Cell Biology & Molecular Genetics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Engagement of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells (ECs) by anti-ICAM coated beads generates vesiculization via cell adhesion molecule (CAM)-mediated endocytosis, a clathrin-/caveolae-independent pathway involving Na+/H+ exchanger 1 (NHE1). ICAM-1 itself plays a key role in transendothelial migration (TEM) of leukocytes, particularly via the transcellular route. This involves endothelial endocytic vesicles that coalesce into transmigration pores, through which leukocytes transmigrate without disrupting EC junctions. The contribution of CAM-mediated endocytosis to the formation of docking sites and vesicular structures supporting TEM was explored in this study. Results show that the ICAM-1/NHE1-dependent CAM-mediated pathway associates with acid sphingomyelinase and ceramide. This supports plasmalemma deformability and cytoskeleton rearrangement, bridging these events to the formation of endothelial docking structures and vesicles involved in leukocyte transmigration.