Global ETD Search

1	An In-vivo Analysis of SLMAP Function in the Postnatal Mouse Myocardium Rehmani, Taha January 2017 (has links) SLMAP is a tail anchored membrane protein that alternatively splices to generate three isoforms, SLMAP1, SLMAP2 and SLMAP3. Previous studies in our lab have shown that the postnatal cardiac-specific overexpression of SLMAP1 results in intracellular vesicle expansion and enhanced endosomal recycling. I generated a postnatal cardiac-specific knockout model using the Cre-Lox system to nullify all three SLMAP isoforms and further evaluate its role in the mouse myocardium. SLMAP knockdown and knockout mouse hearts were analyzed with western blotting and qPCR. I found that only SLMAP3 was nullified and phenotypic evaluation through echocardiography indicated that young and old SLMAP3 knockout animals showed no remarkable changes in cardiac function. Furthermore, challenge with stressor isoproterenol had a similar response to wildtype and knockout mice in cardiac structure and function. Surprisingly the level of expression of SLMAP1 and SLMAP2 was maintained in the myocardium from SLMAP3 deficient mice. Interestingly the machinery involved in endosomal recycling was not impacted by the loss of SLMAP3. These data indicate that loss of SLMAP3 does not alter cardiac structure and function in the postnatal myocardium in the presence of SLMAP1 and SLMAP2. Mouse model SLMAP Cardiac Biology Cardiovascular sciences Cardiac phenotyping Isoproterenol SLMAP Trafficking proteins Knockout model Cre-Lox
2	Role of SLMAP in Endoplasmic Reticulum Stress and Unfolded Protein Response Mahmood, Ahsan 13 August 2013 (has links) Cardiac function is regulated by the molecular components of the sarco/endoplasmic reticulum (ER/SR). Disruptions in homeostatic balance of these proteins and calcium regulation results in activation of ER stress response. Sarcolemmal membrane-associated proteins (SLMAPs) are found in cell membrane, SR/ER, and mitochondria. Overexpression of SLMAP in the myocardium has shown to impair excitation-contraction (E-C) coupling in the transgenic (Tg) mice. ER stress response was examined in Tg mice overexpressing SLMAP in the myocardium. In Tg hearts, changes observed in the expression of proteins involved in ER stress were dependent on the age and sex. SLMAP overexpression results in maladaptive ER stress response, as the mice age. Neonatal cardiomyocytes isolated from the Tg hearts showed decreased viability, upregulation of ER stress response proteins, which were sensitized to thapsigargin-induced stress, and desensitized to palmitate-induced oxidative stress. These findings suggest that normal SLMAP levels are important for proper cardiac function, and cell viability. Protein SLMAP Unfolded Protein Response BiP ER stress ER SR Transgenic mouse cardiac function heart EC coupling
3	A Unique Role for Sarcolemmal Membrane Associated Protein Isoform 1 (SLMAP1) as a Regulator of Cardiac Metabolism and Endosomal Recycling Dewan, Aaraf January 2016 (has links) Altered glucose metabolism is the underlying factor in many metabolic disorders, including diabetes. A novel protein recently linked to diabetes through animal and clinical studies is Sarcolemmal Membrane Associated Protein (SLMAP) but its role in metabolism remains undefined. The data here reveals a novel role for SLMAP isoform1 in glucose metabolism within the myocardium. Neonatal cardiomyocytes (NCMs) harvested from hearts of transgenic mice expressing SLMAP1, presented with increased glucose uptake, glycolytic rate, as well as glucose transporter 4 (GLUT4) expressions with minimal impact on lipid metabolism. SLMAP1 expression markedly increased the machinery required for endosomal trafficking of GLUT4 to the membrane within NCMs, accounting for the observed effects on glucose metabolism. The data here indicates SLMAP1 as a unique regulator of glucose metabolism through endosomal regulation of GLUT4 trafficking and suggests it may uniquely serve as a target to limit cardiovascular disease in metabolic disorders such as diabetes. Metabolism Cardiovascular Disease Glucose Lipid SLMAP GLUT4 Endosome Recycling Heart Trafficking Metabolic disorders Glycolysis Diabetes SNARE Membrane biology Bioenergetics
4	Role of SLMAP in Endoplasmic Reticulum Stress and Unfolded Protein Response Mahmood, Ahsan January 2013 (has links) Cardiac function is regulated by the molecular components of the sarco/endoplasmic reticulum (ER/SR). Disruptions in homeostatic balance of these proteins and calcium regulation results in activation of ER stress response. Sarcolemmal membrane-associated proteins (SLMAPs) are found in cell membrane, SR/ER, and mitochondria. Overexpression of SLMAP in the myocardium has shown to impair excitation-contraction (E-C) coupling in the transgenic (Tg) mice. ER stress response was examined in Tg mice overexpressing SLMAP in the myocardium. In Tg hearts, changes observed in the expression of proteins involved in ER stress were dependent on the age and sex. SLMAP overexpression results in maladaptive ER stress response, as the mice age. Neonatal cardiomyocytes isolated from the Tg hearts showed decreased viability, upregulation of ER stress response proteins, which were sensitized to thapsigargin-induced stress, and desensitized to palmitate-induced oxidative stress. These findings suggest that normal SLMAP levels are important for proper cardiac function, and cell viability. Protein SLMAP Unfolded Protein Response BiP ER stress ER SR Transgenic mouse cardiac function heart EC coupling
5	Phospholamban - Identification of novel interaction partners Kownatzki-Danger, Daniel 03 June 2021 (has links) No description available. 610 Phospholamban Phospholamban knockout SERCA2a Calcium Heart Cardiomyocyte Complexome Profiling APEX2 proximity labeling Proximity proteomics STED superresolution microscopy SLMAP 14-3-3 proteins PLN Medizin (PPN619874732) Kardiologie (PPN619875755)

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