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Articles 1 - 7 of 7
Full-Text Articles in Medical Molecular Biology
Nucleotide P2y₂ Receptor-Dependent Leukocyte-Endothelial Interaction, Spencer E. Thomas
Nucleotide P2y₂ Receptor-Dependent Leukocyte-Endothelial Interaction, Spencer E. Thomas
MSU Graduate Theses
Extracellular nucleotides (ATP, UTP) released from cells act on nucleotide receptors to promote vascular inflammation. Increased leukocyte-endothelial interaction is a hallmark of vascular inflammation. The nucleotide P2Y₂ receptor (P2Y₂R), activated by extracellular ATP≈UTP, plays a role in cardiovascular homeostasis and immune regulation. Moreover, accumulating evidence from studies in vitro and in vivo models have implicated the P2Y₂R in the inflammatory response significantly contributing to the progression and pathogenesis of asthma, atherosclerosis, sepsis, and ischemia. I hypothesized that P2Y₂R activation by UTP, an agonist of the receptor, increased leukocyte rolling and adhesion in the microvasculature from baseline. To test the hypothesis, …
It's A Hard Nacht Life: Understanding How Nlrp12 Ticks, Abbigale Julia Brown
It's A Hard Nacht Life: Understanding How Nlrp12 Ticks, Abbigale Julia Brown
MSU Graduate Theses
The protein NOD- like receptor pyrin domain containing 12 (NLRP12) comes from a family of protein receptors with a wide range of functions including fertility as well as anti-inflammatory properties. The biological role of NLRP12 is poorly understood: research on the mechanisms behind its function and/or activation remains contradictory between different cell models. Current research suggests its involvement in a multi-protein complex named the inflammasome. The alternative hypothesis that has also been proposed is that NLRP12 is not a part of the inflammasome, rather it negatively regulates a transcription factor known as NF-��B down stream of Toll-like receptors. NLRP12 is …
A Biologically Active Tnf-Alpha Inhibitor Fails To Suppress Colitis In Balb/C Mice, Stephanie E. Biel
A Biologically Active Tnf-Alpha Inhibitor Fails To Suppress Colitis In Balb/C Mice, Stephanie E. Biel
MSU Graduate Theses
Tumor necrosis factor a (TNFα), a potent inflammatory cytokine, has long been established as a major driving force for pathologic inflammation. Currently, anti-TNFα therapies are the standard in Inflammatory Bowel Disease (IBD) management; however, one-third of IBD patients fail to respond to anti-TNFα therapies. Previous data from this lab indicate that TNFα Converting Enzyme (TACE) inhibition does not ameliorate colitis in BALB/C mice. Thus, we hypothesized that TNFα is not a critical component in the BALB/C model of colitis. To test this, acute colitis was induced in BALB/C mice by consumption of 5% dextran sulfate sodium (DSS) in drinking water …
Characterization Of The Skeletal Phenotype In Idua-W392x Knock-In Mice: Bone Metabolism Biomarkers, Christina J. Owensby
Characterization Of The Skeletal Phenotype In Idua-W392x Knock-In Mice: Bone Metabolism Biomarkers, Christina J. Owensby
MSU Graduate Theses
Mucopolysaccharidosis Type I (MPS I, Hurlers Syndrome) is a lysosomal storage disease caused by a deficiency of alpha-L-iduronidase (IDUA). IDUA catalyzes the degradation of the two glycosaminoglycans (GAGs); heparin sulfate (HS) and demantan sulfate (DS). The accumulation of HS and DS makes MPS I progressive with inevitable degeneration of multiple organ systems. Accumulated excess of GAGs on the skeletal system causes dysostosis multiplex, atlantoaxial instability, thoracolumbar kyphosis, genu valgum, acetabular dysplasia, and short stature. Skeletal biomarkers of bone formation and bone resorption were compared in wild-type, heterozygous, and IDUAW392X mice. To investigate osteoblast activity, levels of the bone formation marker …
Identification And Characterization Of Dna Repair Snf2/Swi2 Atpases In Tetrahymena Thermophila, Andrew Francis Morin
Identification And Characterization Of Dna Repair Snf2/Swi2 Atpases In Tetrahymena Thermophila, Andrew Francis Morin
MSU Graduate Theses
The Snf2/Swi2 ATPases Rad5 and Rad16 have been shown to play vital roles in a number of DNA repair pathways. In both Saccharomyces cerevisiae and human cell lines, Rad5 homologs (SHPRH, HLTF) have been shown to function in DNA double strand break (DSB) repair along with pathways that repair damage after replication. The function of Rad16, unlike Rad5, has been found only in lower eukaryotes such as Saccharomyces, despite the fact that it plays an essential role in nucleotide excision repair (NER), and more specifically in the repair of silenced areas of the genome. In order to more fully understand …
Systemic Insulin Sensitivity And Skeletal Muscle Akt Signaling In Rats Artificially Selected For Low And High Aerobic Capacity, Kyle Levi Fulghum
Systemic Insulin Sensitivity And Skeletal Muscle Akt Signaling In Rats Artificially Selected For Low And High Aerobic Capacity, Kyle Levi Fulghum
MSU Graduate Theses
The mechanism(s) linking physical inactivity, obesity, and type-II diabetes are unclear. I hypothesized low intrinsic aerobic capacity is associated with reduced systemic insulin sensitivity via skeletal muscle insulin signaling. After 34 generations of selective breeding, high aerobic capacity (HCR) rats exhibited an 8-fold increase in running distance vs low aerobic capacity (LCR) rats (n=14 per group). LCR rats had higher rates of weight gain vs HCR (p<0.05) though food consumption was constant (p=0.86) over a 12-week study. Rats were divided into 4 groups: 1) LCR-Sham Surgery, 2) LCR-Catheterization, 3) HCR-Sham Surgery or 4) HCR-Catheterization (n=7 per group). Euglycemic-hyperinsulinemic clamps on catheterized rats tested insulin sensitivity while sham LCR and HCR were used for basal tissue analysis. Plasma insulin levels did not differ during the clamps, but LCR required lower glucose infusion rates than HCR (p<0.05). Upon insulin stimulation, both absolute and normalized phospho-Akt(Ser473) of soleus muscle were significantly increased in HCR above basal group (p<0.05), but not in LCR. No difference was observed between insulin-stimulated phospho-Akt(Ser473) of HCR and LCR groups . These data support that LCR is linked to a reduction in insulin sensitivity in vivo without impairments of insulin-stimulated skeletal muscle phospho-Akt(Ser473) vs HCR rats.
Tumor Necrosis Factor Alpha Converting Enzyme Inhibition During Acute Colitis In Mice: A Regional Analysis, Brian Maddox
Tumor Necrosis Factor Alpha Converting Enzyme Inhibition During Acute Colitis In Mice: A Regional Analysis, Brian Maddox
MSU Graduate Theses
Tumor Necrosis Factor-a Converting Enzyme (TACE) induces active TNFa and may contribute to the development of colitis in humans. I hypothesized that pharmacological blockade of TNFa production would improve colitis scoring through decreased expression of inflammatory biomarkers. Acute colitis was induced in wild type BALB/c mice using 5% dextran sulfate sodium (DSS) in drinking water for 7 days. TACE inhibition was accomplished through twice daily intraperitoneal injection of DPC- 333 (10mg/kg; BSM Inc.) To determine the effects of TACE blockade during colitis, the following experimental groups (n=6-7/group) were tested: 1) vehicle; 2) DPC-333; 3) 5% DSS and vehicle; and 4) …