Amino Acids, Peptides, and Proteins Commons^™

Leptin Regulates Cd16 Expression On Human Monocytes In A Sex-Specific Manner, Joseph G. Cannon, Gyanendra Sharma, Gloria Sloan, Christiana Dimitropoulou, R. Randall Baker, Andrew Mazzoli, Barbara Kraj, Anthony Mulloy, Miriam Cortez-Cooper

School of Medical Diagnostics & Translational Sciences Publications

Fat mass is linked mechanistically to the cardiovascular system through leptin, a 16 kDa protein produced primarily by adipocytes. In addition to increasing blood pressure via hypothalamic-sympathetic pathways, leptin stimulates monocyte migration, cytokine secretion, and other functions that contribute to atherosclerotic plaque development. These functions are also characteristics of CD16-positive monocytes that have been implicated in the clinical progression of atherosclerosis. This investigation sought to determine if leptin promoted the development of such CD16-positive monocytes. Cells from 45 healthy men and women with age ranging from 20 to 59 years were analyzed. Circulating numbers of CD14++16++ monocytes, which are primary …

Chikungunya Virus Infection Results In Higher And Persistent Viral Replication In Aged Rhesus Macaques Due To Defects In Anti-Viral Immunity, Ilhem Messaoudi, Jennifer Totonchy, Thomas Totonchy, Craig N. Kreklywich, Kristen Haberthur, Laura Springgay, James D. Brien, Michael S. Diamond, Victor R. Defilippis, Daniel N. Streblow

Pharmacy Faculty Articles and Research

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne Alphavirus that causes a clinical disease involving fever, myalgia, nausea and rash. The distinguishing feature of CHIKV infection is the severe debilitating poly-arthralgia that may persist for several months after viral clearance. Since its re-emergence in 2004, CHIKV has spread from the Indian Ocean region to new locations including metropolitan Europe, Japan, and even the United States. The risk of importing CHIKV to new areas of the world is increasing due to high levels of viremia in infected individuals as well as the recent adaptation of the virus to the mosquito species Aedes …

Cytomegalovirus Cc Chemokine Promotes Immune Cell Migration, Jennifer Totonchy, Michael Denton, Craig N. Kreklywich, Takeshi Andoh, Jessica M. Osborn, Daniel Chen, Ilhem Messaoudi, Susan L. Orloff, Daniel N. Streblow

Pharmacy Faculty Articles and Research

Cytomegaloviruses manipulate the host chemokine/receptor axis by altering cellular chemokine expression and by encoding multiple chemokines and chemokine receptors. Similar to human cytomegalovirus (HCMV), rat cytomegalovirus (RCMV) encodes multiple CC chemokine-analogous proteins, including r129 (HCMV UL128 homologue) and r131 (HCMV UL130 and MCMV m129/130 homologues). Although these proteins play a role in CMV entry, their function as chemotactic cytokines remains unknown. In the current study, we examined the role of the RCMV chemokine r129 in promoting cellular migration and in accelerating transplant vascular sclerosis (TVS) in our rat heart transplant model. We determined that r129 protein is released into culture …

Hcmv Pus28 Initiates Pro-Migratory Signaling Via Activation Of Pyk2 Kinase, Jennifer Totonchy, Susan Varnum, Ryan Melnychuk, Patricia Smith, Ljiliana Pasa-Tolic, Janani I. Shutthanadan, Daniel N. Streblow

Pharmacy Faculty Articles and Research

Background: Human Cytomegalovirus (HCMV) has been implicated in the acceleration of vascular disease and chronic allograft rejection. Recently, the virus has been associated with glioblastoma and other tumors. We have previously shown that the HCMV-encoded chemokine receptor pUS28 mediates smooth muscle cell (SMC) and macrophage motility and this activity has been implicated in the acceleration of vascular disease. pUS28 induced SMC migration involves the activation of the protein tyrosine kinases (PTKs) Src and Focal adhesion kinase as well as the small GTPase RhoA. The PTK Pyk2 has been shown to play a role in cellular migration and formation of cancer, …

Fetal Cocaine Exposure Causes Epigenetic Changes In The Rat Heart, Kurt D. Meyer

Loma Linda University Electronic Theses, Dissertations & Projects

Cocaine abuse continues to be prevalent in the United States and other industrialized nations, in addition to the negative health effects that cocaine abuse has on the user, a mother who uses cocaine while pregnant also exposes the developing fetus to cocaine. Although there have been many studies of the effects of cocaine on the adult heart, studies of cocaine on the fetal heart and its potential delayed pathophysiological effects on cardiac function in adult offspring are extremely limited. The studies of the present project sought to enhance the understanding of the effect of cocaine exposure on the fetal heart …

Human Cytomegalovirus Us28: A Functionally Selective Chemokine Binding Receptor, Jennifer Totonchy, Jay A. Nelson, Daniel N. Streblow

Pharmacy Faculty Articles and Research

The Human Cytomegalovirus (HCMV)-encoded chemokine receptor US28 is the most well-characterized of the four chemokine receptor-like molecules found in the HCMV genome. US28 been studied as an important virulence factor for HCMV-mediated vascular disease and, more recently, in models of HCMV-associated malignancy. US28 is a rare multi-chemokine family binding receptor with the ability to bind ligands from two distinct chemokine classes. Ligand binding to US28 activates cell-type and ligand-specific signaling pathways leading to cellular migration, an example receptor functional selectivity. Additionally, US28 has been demonstrated to constitutively activate PLC and NFkB. Understanding the structure/function relationships between US28, its ligands and …

Rat Cytomegalovirus Infection Depletes Mhc Ii In Bone Marrow Derived Dendritic Cells, Carmen C. Baca Jones, Craig N. Kreklywich, Ilhem Messaoudi, Jennifer Totonchy, Erin Mccartney, Susan L. Orloff, Jay A. Nelson, Daniel N. Streblow

Pharmacy Faculty Articles and Research

While cytomegalovirus (CMV) infects and replicates in a multitude of cell types, the ability of the virus to replicate in antigen presenting cells (APCs) is believed to play a critical role in the viral dissemination and latency. CMV infection of APCs and manipulation of their function is an important area of investigation. CMV down regulation of MHC II is reportedly mediated by the HCMV proteins US2, US3, UL83, UL111a (vIL10) or through the induction of cellular IL10. In this study, we demonstrate that rat CMV (RCMV) significantly reduces MHC II expression by mechanisms that do not involve orthologues of the …

Differential Ligand Binding To A Human Cytomegalovirus Chemokine Receptor Determines Cell Type-Specific Motility, Jennifer Totonchy, Ryan Melnychuk, Patricia P. Smith, Joshua Powell, Laurel Hall, Victor R. Defilippis, Klaus Fruh, Martine Smit, David D. Schlaepfer, Jay A. Nelson, Daniel N. Streblow

Pharmacy Faculty Articles and Research

While most chemokine receptors fail to cross the chemokine class boundary with respect to the ligands that they bind, the human cytomegalovirus (HCMV)-encoded chemokine receptor US28 binds multiple CC-chemokines and the CX3Cchemokine Fractalkine. US28 binding to CC-chemokines is both necessary and sufficient to induce vascular smooth muscle cell (SMC) migration in response to HCMV infection. However, the function of Fractalkine binding to US28 is unknown. In this report, we demonstrate that Fractalkine binding to US28 not only induces migration of macrophages but also acts to inhibit RANTES-mediated SMC migration. Similarly, RANTES inhibits Fractalkine-mediated US28 migration in macrophages. While US28 binding …

Radiation-Induced Glutamate Transport Alterations In Neuron-Astrocyte Coupling, Martha Celia Sanchez

Loma Linda University Electronic Theses, Dissertations & Projects

Exposure of the central nervous system (CNS) to ionizing radiation is known to result in behavioral, cognitive, and motor deficits - effects similar to those seen in many neurodegenerative disorders. Neurons and astrocytes, two principal cell types in the brain, coexist as an interdependent metabolic unit via the neurotransmitter glutamate. Disruption of this metabolic coupling would have widespread effects within the CNS, therefore it is hypothesized that ionizing radiation impairs glutamate transport and metabolism, and increases oxidative stress, ultimately impairing neuron-astrocyte coupling. We propose to investigate the mechanism and determine the impetus for radiation-induced neurotoxicity by measuring the temporal sequence …

Mouse Cytomegalovirus M33 Is Necessary And Sufficient In Virus-Induced Vascular Smooth Muscle Cell Migration, Ryan Melnychuk, Patsy Smith, Craig N. Kreklywich, Franziska Ruchti, Jennifer Totonchy, Laurel Hall, Lambert Loh, Jay A. Nelson, Susan L. Orloff, Daniel N. Streblow

Pharmacy Faculty Articles and Research

Mouse cytomegalovirus (MCMV) encodes two potential seven-transmembrane-spanning proteins with homologies to cellular chemokine receptors, M33 and M78. While these virus-encoded chemokine receptors are necessary for the in vivo pathogenesis of MCMV, the function of these proteins is unknown. Since vascular smooth muscle cell (SMC) migration is of critical importance for the development of atherosclerosis and other vascular diseases, the ability of M33 to promote SMC motility was assessed. Similar to human CMV, MCMV induced the migration of mouse aortic SMCs but not mouse fibroblasts. To demonstrate whether M33 was required for MCMV-induced SMC migration, we employed interfering-RNA technology to specifically …

Human Cytomegalovirus Chemokine Receptor Us28-Induced Smooth Muscle Cell Migration Is Mediated By Focal Adhesion Kinase And Src, Daniel N. Streblow, Jennifer Totonchy, Patsy Smith, Ryan Melnychuk, Laurel Hall, Dora Pancheva, Martine Smit, Paola Casarosa, David D. Schlaepfer, Jay A. Nelson

Pharmacy Faculty Articles and Research

The human cytomegalovirus-encoded chemokine receptor US28 induces arterial smooth muscle cell (SMC) migration; however, the underlying mechanisms involved in this process are unclear. We have previously shown that US28-mediated SMC migration occurs by a ligand-dependent process that is sensitive to proteintyrosine kinase inhibitors. We demonstrate here that US28 signals through the non-receptor protein-tyrosine kinases Src and focal adhesion kinase (FAK) and that this activity is necessary for US28-mediated SMC migration. In the presence of RANTES (regulated on activation normal T cell expressed and secreted), US28 stimulates the production of a FAK Src kinase complex. Interestingly, Src co-immunoprecipitates with US28 in …

Effects Of A Serine 364 To Proline Mutation Of The Connexin43 Protein In Transgenic Mice, Chia-Ling Nhan-Chang

Loma Linda University Electronic Theses, Dissertations & Projects

[Abstract Not Included]

Regulation Of Connexin43 By Phosphorylation, Maithili M. Shah

Loma Linda University Electronic Theses, Dissertations & Projects

Gap junctions play a crucial role in embryogenesis, especially of the heart where connexin43 is thought to be important for its formation as well as synchronized contraction. Several reports have shown that connexin43 protein is phosphorylated on serine residues in vitro and in vivo.

Studies performed in our laboratory have demonstrated that cell-to-cell communication in cells expressing connexin43 can be controlled rapidly and reversibly by microinjection of active protein kinases or phosphatases that target serine or threonine residues. Phosphorylation by cAMP-dependent protein kinase (PKA) seems to favor channel opening, whereas the effect of protein kinase C (PKC) on channel gating …

Effect Of Photoperiod On Developmental Morphology And Enolase Isoenzyme Immunohistochemistry In Rat And Djungarian Hamster Superficial Pineal Glands, Chalmer D. Mcclure

Loma Linda University Electronic Theses, Dissertations & Projects

The best understood functional activity of the pineal gland is its diurnal production of melatonin in response to environmental lighting cues. Several enzymes of the melatonin pathway respond to daily photoperiod changes, for example hydroxyindole-O-methyltransferase (HIOMT) and serotonin N-acetyltransferase (SNAT). Increased levels of the glycolytic enzyme neuron-specific enolase (NSE) are thought to reflect increased physiological demands placed on neurons and neuroendocrine tissues. Homodimer non-neuronal enolase isoenzyme (NNE) is immunolocalized to cells, and the hybrid enolase (consisting of subunits from NSE and NNE) has been seen in cerebellar stellate and basket cells. Although not rate limiting, concentrations of both NSE and …

Collagen Binding Proteins Derived From The Embryonic Fibroblast Cell Surface Recognize Arginine-Glycine-Aspartic Acid, Roy C. Ogle, Charles D. Little

School of Medical Diagnostics & Translational Sciences Publications

Several cell surface proteins (Mr = 120,000, 90,000, 63,000 and 47,000) apparently integral to embryonic fibroblast plasma membranes were extracted with detergent and isolated by collagen affinity chromatography. Certain of these proteins (Mr = 120,000, 90,000, and 47,000) were specifically eluted from collagen affinity columns by synthetic peptides containing the amino acid sequence arginyl-glycyl-aspartic acid (RGD). These data show that a number of collagen binding proteins exist on the embryonic fibroblast cell surface. Some of the proteins may be collagen receptors binding to RGD sequences in the collagen molecule while at least one of the proteins (Mr = 63,000) recognizes …

Laminin Receptors For Neurite Formation, H. K. Kleinman, Roy C. Ogle, F. B. Cannon, C. D. Little, T. M. Sweeney, L. Luckenbill-Edds

School of Medical Diagnostics & Translational Sciences Publications

Laminin, a basement membrane glycoprotein promotes both cell attachment and neurite outgrowth. Separate domains on laminin elicit these responses, suggesting that distinct receptors occur on the surface of cells. NG108-15 neuroblastoma-glioma cells rapidly extend long processes in the presence of laminin. We report here that 125I-labeled laminin specifically binds to these cells and to three membrane proteins of 67, 110, and 180 kDa. These proteins were isolated by affinity chromatography on laminin-Sepharose. The 67-kDa protein reacted with antibody to the previously characterized receptor for cell attachment to laminin. Antibodies to the 110-kDa and 180-kDa bands demonstrated that the 110-kDa protein …

The Synthesis And Evaluation Of The Cardiovascular Activity Of Novel Imidazole Ring Systems, Joseph E. De Los Angeles

Chemistry & Biochemistry Theses & Dissertations

An investigation was undertaken to synthesize and evaluate the cardiovascular activity of two imidazole ring systems. Imidazoles with hypotensive activity would provide novel potential antihypertensive drugs. These novel structures may also find use as chemical probes in the study of the cardiovascular system and as prototypes for other potential cardiovascular agents.

The histamine derivative, 7,7-dipyridyl-4,5,6,7-tetrahydroimidazo-[4,5-c]pyridine (ligand l), was demonstrated to possess significant hypotensive activity in laboratory rats. A 15 mg/Kg dose of ligand 1 produces a statistically significant decrease in blood pressure when injected IP. This hypotensive effect is also associated with marked increase in heart rate. Although compound 1 …