Cell and Developmental Biology Commons^™

Transcriptional Regulation Of Profilin Is Required For Drosophila Larval Wound Closure, Amanda Brock

Dissertations and Theses (Open Access)

Injury is an inevitable part of life, making wound healing essential for survival. In postembryonic skin, wound closure requires that epidermal cells recognize the presence of a gap and change their behavior to migrate across it. In Drosophila larvae, wound closure requires two signaling pathways (the Jun N-terminal kinase (JNK) pathway and the Pvr receptor tyrosine kinase signaling pathway) and regulation of the actin cytoskeleton. In this and other systems, it remains unclear how the signaling pathways that initiate wound closure connect to the actin regulators that help execute wound- induced cell migrations. Here we show that chickadee, which encodes …

Platelets And Anti-Angiogenic Resistance In Ovarian Carcinoma, Justin N. Bottsford-Miller

Dissertations and Theses (Open Access)

Background: Resistance to targeted anti-angiogenic therapy is a growing clinical concern given the disappointing clinical impact of anti-angiogenic. Platelets represent a component of the tumor microenvironment that are implicated in metastasis and represent a significant reservoir of angiogenic regulators. Thrombocytosis has been shown to be caused by malignancy and associated with adverse clinical outcomes, however the causal connections between these associations remain to be identified.

Materials and Methods: Following IRB approval, patient data were collected on patients from four U.S. centers and platelet levels through and after therapy were considered as indicators of recurrence of disease. In vitro effects of …

Identification And Analysis Of A Novel Role For The To Usled-Like Kinase In Regulating Mitotic Spindle Dynamics, Jason R. Ford

Dissertations and Theses (Open Access)

Deregulation of kinase activity is one example of how cells become cancerous by evading evolutionary constraints. The Tousled kinase (Tsl) was initially identified in Arabidopsis thaliana as a developmentally important kinase. There are two mammalian orthologues of Tsl and one orthologue in C. elegans, TLK-1, which is essential for embryonic viability and germ cell development. Depletion of TLK-1 leads to embryonic arrest large, distended nuclei, and ultimately embryonic lethality. Prior to terminal arrest, TLK-1-depleted embryos undergo aberrant mitoses characterized by poor metaphase chromosome alignment, delayed mitotic progression, lagging chromosomes, and supernumerary centrosomes.

I discovered an unanticipated requirement for TLK-1 …

The Role Of Acetyl-Coa Carboxylase In The Survival Of Trypanosoma Brucei During Infection, Ciara Mcknight

All Theses

This master's thesis focuses on how disruption of fatty acid metabolism affects both host adaptation and immune evasion in the deadly eukaryotic parasite, Trypanosoma brucei. In Chapter 1, I review the current literature on African trypanosomiasis, fatty acid synthesis, immune evasion, and lipid metabolism. In Chapter 2, I investigate how disruption of the fatty acid synthesis pathway affects the parasite's ability to evade the host immune defenses. When T. brucei acetyl-CoA carboxylase (TbACC) is knocked down by RNA interference (RNAi), fluid phase and receptor mediated endocytosis pathways are greatly affected, suggesting that fatty acid synthesis is necessary for both endocytic …

Synergistic Effects Of Nanosecond Pulsed Electric Fields Combined With Low Concentration Of Gemcitabine On Human Oral Squamous Cell Carcinoma In Vitro, Jing Wang, Jinsong Guo, Shan Wu, Hongqing Feng, Shujun Sun, Jie Pan, Jue Zhang, Stephen J. Beebe

Bioelectrics Publications

Treatment of cancer often involves uses of multiple therapeutic strategies with different mechanisms of action. In this study we investigated combinations of nanosecond pulsed electric fields (nsPEF) with low concentrations of gemcitabine on human oral cancer cells. Cells (Cal-27) were treated with pulse parameters (20 pulses, 100 ns in duration, intensities of 10, 30 and 60 kV/cm) and then cultured in medium with 0.01 mu g/ml gemcitabine. Proliferation, apoptosis/necrosis, invasion and morphology of those cells were examined using MTT, flow cytometry, clonogenics, transwell migration and TEM assay. Results show that combination treatments of gemcitabine and nsPEFs exhibited significant synergistic activities …

Cell Bioenergetics In Leghorn Male Hepatoma Cells And Immortalized Chicken Liver Cells In Response To 4-Hydroxynonenal Induced Oxidative Stress, Alissa Laura Piekarski

Graduate Theses and Dissertations

Bioenergetic mechanisms responsible for ATP production are essential in carrying out maintenance and cell-specific functions. In this study, hepatocytes (liver cells) were used to test both endogenous and exogenous stress on cellular respiration. The secondary lipid peroxide, 4-hydroxynonenal (HNE), was used because it alters bioenergetics by increasing mitochondrial proton leak that attenuates mitochondrial radical production and, therefore, endogenous oxidative stress. The major objective of this study was to demonstrate effects of HNE-induced oxidative stress on avian hepatocyte bioenergetics. Various chemical which help enable the determination of oxygen (O2) consumption linked to ATP synthesis (oligomycin), maximal O2 consumption (FCCP), and proton …

Peptoid Based Slide Coatings For Disease Detection Via Elisa Microarray Analysis, Melissa Lea Hebert

Graduate Theses and Dissertations

Poly-N-substituted glycines (peptoids) are a very versatile family of synthetic molecules that can be customized for any number of applications. In this study, we chose to use peptoids as a foundation for sandwich ELISA microarray analysis with a long term goal of creating an early detection device for complex diseases such as cancer. The peptoids were designed to self-assemble into microspheres to be used in coatings on the surface of the microarray substrates to increase the surface area available for antibody attachment. This increased antibody density would lead to an increase in the microarray analysis sensitivity and dynamic range. Studies …

An Analysis Of The Redox Properties And Stability Of Chlamydomonas Reinhardtii Cytochrome F, Cytochrome C6, And Mutants Thereof, Nicole Lynn Vanderbush

Graduate Theses and Dissertations

This body of work presents mutagenesis studies conducted on two c-type cytochromes from Chlamydomonas reinhardtii. Cytochrome f, a unique c-type cytochrome, is investigated in regards to its redox potential, the dependence of the redox potential, and the thermal stability of the protein. The mutations made were Y1F, Y9F, Y160F, Y160L, R156L, and R156K. The residues that were mutated surround the heme. It was found that, relative to the wild-type, only the Y160L and R156 mutants showed any difference in midpoint potential at pH 7. Wild-type and mutants both had a midpoint potential that was dependent upon pH indicating that none …

Plant Lectin Can Target Receptors Containing Sialic Acid, Exemplified By Podoplanin, To Inhibit Transformed Cell Growth And Migration, Jhon Ochoa-Alvarez, Harini Krishnan, Yongquan Shen, Nimish Acharya, Min Han, Dean Mcnulty, Hitoki Hasegawa

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Cancer is a leading cause of death of men and women worldwide. Tumor cell motility contributes to metastatic invasion that causes the vast majority of cancer deaths. Extracellular receptors modified by α2,3-sialic acids that promote this motility can serve as ideal chemotherapeutic targets. For example, the extracellular domain of the mucin receptor podoplanin (PDPN) is highly O-glycosylated with α2,3-sialic acid linked to galactose. PDPN is activated by endogenous ligands to induce tumor cell motility and metastasis. Dietary lectins that target proteins containing α2,3-sialic acid inhibit tumor cell growth. However, anti-cancer lectins that have been examined thus far target receptors …

Identification Of Ebs1, Lsm6 And Nup159 As Suppressors Of Spt10 Effects At Adh2 In Saccharomyces Cerevisiae Suggests Post-Transcriptional Defects Affect Mrna Synthesis, Bradley Anderson, Carrie Ann May, Clyde L. Denis

New Hampshire Agricultural Experiment Station Publications

Suppression of the effects of an spt10 mutation on ADH2 expression is a phenotype shared by a small number of genes whose protein products are either components of the CCR4-NOT complex required for mRNA deadenylation and degradation (CCR4, CAF1, NOT4) or have been shown to interact with the complex (DBF2, SRB9, SRB10). In this work, we conducted a screen for additional suppressors of spt10 at ADH2 to identify new factors related to CCR4 function. In addition to reisolating ccr4 and caf1 alleles, three previously unidentified suppressors …

Optimizing Protocols For The Derivation Of Primary Cultures From Mammalian Tissue, Eduardo Ramirez, Natzidielly Lerma, Paloma Valenzuela, Karla Parra, Courteny L. Becerril, Irving Miramontes, Howard West, Cynthia Rodriguez, Giulio Francia

COURI Symposium Abstracts, Summer 2012

The isolation of primary cell cultures from fresh mammalian tissue is a major interest of our laboratory. Thus, the ability to generate cancer cell lines from cancer tissue, or to generate non-malignant cultures form the host stroma surrounding a tumor, allows us to develop new laboratory models to study the behavior of cancer cells and its microenvironment. We report our proof of principle study on optimizing the derivation of primary culture, using rat tissues as a model. Thus, rat kidney and rat skin samples were isolated, minced with surgical blades, and then incubated with an enzyme digestion cocktail (Collagenase III- …

Inhibitors Of Polyisoprenylated Methylated Protein Methyl Esterase (Pmpmease) Cause Neurodegeneration By Altering Microtubules And Gβγ In Pc12 Cells, Jose A. Rivas Jr., Rebekah M. Bach, Jessica Martinez-Jurado, Jorge A. Siera-Fonseca, Sukla Roychowdhury

COURI Symposium Abstracts, Summer 2012

Neurodegeneration, a progressive loss of nerve cells (neurons), occurs in many neurological disorders including Alzheimer’s disease, Parkinson’s disease, Schizophrenia and drug addiction. Disruption of Microtubules (MTs), a major component of cytoskeleton and aggregation of proteins associated with them is the hallmark of neurodegeneration. Gβγ, an important component of G protein signaling has been shown to induce neurite outgrowth of PC12 cells by interacting with microtubules. The goal of the present study is to understand whether interfering with Gβγ-MT mediated pathway causes neurodegeneration. Because prenylation of γ subunits is important for the interaction of Gβγ with MTs, we used inhibitors (L-23 …

Characterization Of The Infectivity Of Non-Replicating Human Immunodeficiency Virus (Hiv)-Derived Viral Vectors., Vanessa E. Rodriguez, Manuel Llano, Luis Valdes

COURI Symposium Abstracts, Summer 2012

The ability of HIV-derived viral vectors to integrate genes of interest into the host genome causing permanent phenotypic modifications makes them excellent tools in gene therapy. However, integration also causes insertional mutagenesis and controlling integration site selection will increase the biosafety of these molecular tools. HIV DNA integration site selection is influenced by LEDGF/p75, a chromatin-bound cellular protein that interacts with the viral enzyme integrase through the integrase binding domain (IBD). Integrase catalyzes viral DNA integration and non-covalently associates with the HIV genome forming the pre-integration complex (PIC). Therefore, interaction of chromatin-bound LEDGF/p75 with the PIC-associated integrase tethers the HIV …

Gβγ-Microtubule Interaction And Neurodegeneration, Jane K. Martinez, Jorge Sierra, Sukla Roychowdhury Ph.D.

COURI Symposium Abstracts, Summer 2012

Aberrant organization of microtubules (MTs) is known to be a feature of neurodegeneration, which occurs in many neurological disorder including Alzheimer’s disease, Parkinson’s disease, neuropsychiatric illness such as schizophrenia, and drug addiction. Previously, Gβγ, an important component of G protein-coupled signaling pathways, has been shown to regulate neurite outgrowth by interacting with MTs. The aim of the present study is to understand the Gβγ regulation of MT assembly and its relation to neurodegeneration, using GRK-ct peptide (consists of the carboxy terminus of G protein-coupled-receptor kinase) which is known to inhibit Gβγ-dependent signaling by binding to and sequestering Gβγ. PC12 cells …

Messenger Mrna Analysis As A Means To Identify Mechanisms Of Cancer Drug Resistance, Courtney L. Becerril, Irving Miramontes, Jiselle Del Cid, Natzidielly Lerma, Karla Parra, Eduardo D. Ramirez, Howard West, Paloma Valenzuela, Cynthia Rodriguez, Giulio Francia

COURI Symposium Abstracts, Summer 2012

On principal approach to identify the mechanisms by which cancers escape from anti-cancer therapies is the analysis of messenger RNAs (mRNAs) in those tumor cells that survive treatment. Thus, by studying Her-2 positive human breast tumor cells that survived anti-Her-2 based therapies (i.e., using anti-Her-2 antibody) we observed the 3-fold or greater overexpression of Vascular Endothelial Growth Factor (VEGF) mRNA. Similarly, by studying the mRNAs of tumor cell cultures resistant to chemotherapy (such as cisplatin), we found that low levels of mRNAs for DNA mismatch repair genes correlates with drug resistance. These results suggest that two possible strategies of sensitizing …

Protein Expression Analysis Of Cell Lines Derived From Drug Resistant Tumors, Paloma Valenzuela, Karla Parra, Natzidielly Lerma, Courtney Becerril, Eduardo Ramirez, Irving Miramontes, Howard West, Cynthia Rodriguez, Yang Li, Jianying Zhang, Giulio Francia

COURI Symposium Abstracts, Summer 2012

There are a number of effective treatments for breast cancer, including chemotherapy and targeted strategies such as the use of the Her-2 targeting drugs lapatinib and trastuzumab. However, in a number of cases, tumors that initially respond to therapy eventually develop drug resistance, leading to the relapse of the disease. By studying protein levels in different drug resistant variants, we have observed two mechanisms by which drug resistance may develop. Thus, some Her-2 human breast cancer cells (e.g., MDA-MB-231H2N) treated with the clinically used trastuzumab agent, can escape therapy by shedding, or losing, the target Her-2 protein. Similarly, EMT-6 mouse …

Evaluating Ceramide Analogs, 5-Lipoxygenase Expression, And Lipid Raft Biology In Breast Cancer, Jiselle Del Cid, Debarshi Roy, Atasi De Chatterjee, Karla Parra, Howard West, Guido Bocci, Cynthia Rodriguez, Siddhartha Das, Giulio Francia

COURI Symposium Abstracts, Summer 2012

To investigate the role of lipid rafts in the biology of breast cancer cells, we designed a human breast cancer cell line panel (using MCF-7, MDA-MB-231, and HCC1419 cells) to test the anti-tumor impact of new ceramide analogs. Our aim is to use such a screening to ultimately develop a project to investigate the role of 5-lipoxygenase enzyme on the behavior of breast cancer cells, including MDA-MB231 that express 5-lipoxygenase and MCF-7 which do not, and to ask whether ceramide analogs can have an impact on this behavior.

To date, we have evaluated three ceramide analogs, termed C2, C6 and …

Development Of New Models To Study Human Her-2 Positive Breast Cancer, Howard J. West, Karla Parra, Natzidielly Lerma, Paloma Valenzuela, Eduardo Ramirez, Courtney L. Becerril, Irving Miramontes, Elizabeth Gamez, Cynthia Rodriguez, Guido Bocci, Giulio Francia

COURI Symposium Abstracts, Summer 2012

To study the evolution of human Her-2 positive breast cancer, we evaluated a model of three dimensional spheroid co-culture using H2N human breast cancer cells that express high amounts of Her-2 protein, with the Her-2 negative MDA-231 cells. Human HCC1419, which can form compact spheroids, were used as controls. In tissue culture plates, H2N cells were found to have a doubling rate of about 48 hours, compared to around 144 hours for MDA231. Since H2N cells were engineered to express a fluorescent protein, we could note that these cells did not immediately overgrow the non-fluorescent MDA231 cells in a mixed …

Insights Into The Role Of The N-Terminus Of The Neuronal Glycine Transporter 2, Diego A. Escobar-Garcia, Ana Garibay, Miryam Pando, Manuel Miranda

COURI Symposium Abstracts, Summer 2012

Hyperekplexia is distinguished by exaggerated muscle tension, sudden shock and even death in response to touch/acoustic stimuli. Genetic analysis showed that mutations on glycinergic proteins on the presynaptic neurons are responsible for the attacks. Mutations in the Glycine Transporter 2 (GlyT2) have been suggested to be the second major cause of hyperekplexia. The GlyT2 consist of twelve transmembrane domains, a 201 amino acid long N-terminus and a shorter C-terminus, both intracellular. Dysfunction of this transporter prevents the intake of glycine from the synapse back to the presynaptic neuron. Our goal is to better understand the role of N-terminus on protein …

Cytotoxic Effects Of Creosote (Larrea Tridentata) Plant Extracts On Human Lymphoma Cells Lines, Emanuel Cordero, Yahaira Santiago, Carolina Lema, Armando Varela-Ramirez, Renato J Aguilera

COURI Symposium Abstracts, Summer 2012

Larrea tridentata also known as Creosote is a North American shrub, whose leave extracts are proposed to contain anti-cancer properties. The main metabolite in this plant is the nordihydroguaiaretic acid (NDGA) has been shown to have anti-neoplastic, anti-viral and anti-inflammatory properties. NDGA is a strong anti-oxidant that can scavenge or inhibit reactive oxygen spices production, stimulate nitric oxide production, increase immune function, enhance central nervous system function, and prevent cardiovascular or other diseases. Although extracts from this plant are currently used in Mexico as an herbal medicine, the Food and Drug Administration and Health Canada have issued health hazard warming …

In Vitro Evaluation Of Human Her2-Positive Breast Cancer Cells, Karla Parra, Howard West, Paloma Valenzuela, Eduardo D. Ramirez, Natzidielly Lerma, Courtney Becerril, Irving Miramontes, Cynthia M. Rodriguez, Guido Bocci, Giulio Francia

COURI Symposium Abstracts, Summer 2012

One in four cases of breast cancer shows over expression of the Her-2 protein, and there is an urgent need to improve therapies for this disease. We have evaluated two Her-2 positive human breast cancer cell lines, MDA-231H2N and HCC1419. MDA-231 human breast cancer cell, which are Her-2 negative, were used as a control. The cell lines were evaluated in vitro for their relative growth rate, their growth under reduced (i.e. 3% serum) conditions, or as spheroid cultures, and for their sensitivity to drugs such as ceramide analogs and tyrosine kinase inhibitors (i.e. CLM3, CLM29, and CLM94) that are being …

Identification Of Two Functional Sumo Interacting Motifs (Sims) In The Non-Structural Protein Of Influenza A Virus Ns1a, Lorellie M. Lewis, German Rosas-Acosta

COURI Symposium Abstracts, Summer 2012

We have previously shown that the non-structural protein of Influenza A virus NS1A is post-translationally modified by conjugation of the Small Ubiquitin-like MOdifier (SUMO). Our functional studies have also demonstrated that SUMO conjugation (SUMOylation) affects NS1A's ability to neutralize the cellular interferon response of the host cell and other functions associated to NS1A. Importantly, we have also shown that influenza infections trigger a global increase in cellular SUMOylation and have recently demonstrated that such an increase is mediated by NS1A. This observation led us to investigate the molecular mechanism endowing NS1A with the ability to increase global cellular SUMOylation. Sequence …

Tissue Specific Porcupine Deletion Reveals A Novel Role For Ectodermal Wnts In Musculotendon Development, Aaron P. Smith

Theses and Dissertations

The Wnt family of secreted proteins consists of 19 family members (in the mouse) and is known to signal through multiple pathways that regulate crucial processes in the development of almost all tissues. Dissecting the roles of individual Wnts has been hampered due to functional redundancy that exists between family members. We made use of a conditional allele of the acyltransferase, Porcupine (Porcn), that is required for the secretion of all Wnt ligands, and the Msx2Cre deleter to eliminate the secretion of all Wnt ligands from the ventral limb ectoderm, ventral abdominal ectoderm, and urogenital ectoderm. Phenotypically the …

Delayed Expression Of Cell Cycle Proteins Contributes To Astroglial Scar Formation And Chronic Inflammation After Rat Spinal Cord Contusion, Junfang Wu, Ahdeah Pajoohesh-Ganji, Bogdan A. Stoica, Michael Dinizo, Kelsey Guanciale, Alan I. Faden

Anatomy and Regenerative Biology Faculty Publications

Background

Traumatic spinal cord injury (SCI) induces secondary tissue damage that is associated with astrogliosis and inflammation. We previously reported that acute upregulation of a cluster of cell-cycle-related genes contributes to post-mitotic cell death and secondary damage after SCI. However, it remains unclear whether cell cycle activation continues more chronically and contributes to more delayed glial change. Here we examined expression of cell cycle-related proteins up to 4 months following SCI, as well as the effects of the selective cyclin-dependent kinase (CDKs) inhibitor CR8, on astrogliosis and microglial activation in a rat SCI contusion model.

Methods

Adult male rats were …

The Human Phosphotyrosine Signaling Network: Evolution And Hotspots Of Hijacking In Cancer., Lei Li, Chabane Tibiche, Cong Fu, Tomonori Kaneko, Michael F. Moran, Martin Schiller, Shawn Shun-Cheng Li, Edwin Wang

Life Sciences Faculty Research

Phosphotyrosine (pTyr) signaling, which plays a central role in cell-cell and cell-environment interactions, has been considered to be an evolutionary innovation in multicellular metazoans. However, neither the emergence nor the evolution of the human pTyr signaling system is currently understood. Tyrosine kinase (TK) circuits, each of which consists of a TK writer, a kinase substrate, and a related reader, such as Src homology (SH) 2 domains and pTyr-binding (PTB) domains, comprise the core machinery of the pTyr signaling network. In this study, we analyzed the evolutionary trajectories of 583 literature-derived and 50,000 computationally predicted human TK circuits in 19 representative …

The Effects Of Cytokinin On The Transcriptional Regulation Of Pin Expression In Arabidopsis Thaliana, Elizabeth Burgess

Honors Theses and Capstones

The processes of cell division and differentiation are critical to the development of any multicellular organism. During the formation of plant roots these processes take place at a region of the root tip called the meristem. Cytokinin and auxin are two plant growth hormones that influence this process. Although these two growth hormones are both necessary they also appear in many ways to have an antagonistic relationship. As meristematic root cells undergo differentiation they cease dividing. It has been proposed that the size of the root meristem and thus the overall rate of root growth are determined by the balance …

Dietary Analysis And Epigenetic Comparisons Of Drosphila Melanogaster Through Multiple Generations, Xu (Kevin) F. Zheng

Holster Scholar Projects

Nutrition and the lack thereof has been a demanding issue in both the undeveloped and developed country. The unbalance diet between healthy and unhealthy diet has led to many of the problems presented in society such as obesity, heart disorders, and loss of longevity. It is now known that calorie may not provide the most accurate information in terms of the lifestyle and the well-being of humans. Rather the composition of the calorie is what becomes integral in people's understanding of the effect of food physiologically. With this knowledge, we seek to use a Drosophila melanogaster as a model organism …

Mecp2 Binds To Nucleosome Free (Linker Dna) Regions And To H3k9/H3k27 Methylated Nucleosomes In The Brain, Anita A. Thambirajah, Marlee K. Ng, Lindsay J. Frehlick, Andra Li, Jason J. Serpa, Evgeniy V. Petrotchenko, Begonia Silva-Moreno, Kristal K. Missiaen, Christoph H. Borchers, J. Adam Hall, Ryan Mackie, Frank Lutz, Brent E. Gowen, Michael Hendzel, Philippe T. Georgel, Juan Ausió

Biological Sciences Faculty Research

Methyl-CpG-binding protein 2 (MeCP2) is a chromatin-binding protein that mediates transcriptional regulation, and is highly abundant in brain. The nature of its binding to reconstituted templates has been well characterized in vitro. However, its interactions with native chromatin are less understood. Here we show that MeCP2 displays a distinct distribution within fractionated chromatin from various tissues and cell types. Artificially induced global changes in DNA methylation by 3-aminobenzamide or 5-aza-2′-deoxycytidine, do not significantly affect the distribution or amount of MeCP2 in HeLa S3 or 3T3 cells. Most MeCP2 in brain is chromatin-bound and localized within highly nuclease-accessible regions. We …

An Analysis Of The Myocardial Transcriptome In A Mouse Model Of Cardiac Dysfunction With Decreased Cholinergic Neurotransmission, Ashbeel Roy, Aline Lara, Diogo Guimaraes, Rita Pires, Eneas R. Gomes, David E. Carter, Marcus V. Gomez, Silvia Guatimosim, Vania F. Prado, Marco A. M. Prado, Robert Gros

Anatomy and Cell Biology Publications

Autonomic dysfunction is observed in many cardiovascular diseases and contributes to cardiac remodeling and heart disease. We previously reported that a decrease in the expression levels of the vesicular acetylcholine transporter (VAChT) in genetically-modified homozygous mice (VAChT KDHOM) leads to decreased cholinergic tone, autonomic imbalance and a phenotype resembling cardiac dysfunction. In order to further understand the molecular changes resulting from chronic long-term decrease in parasympathetic tone, we undertook a transcriptome-based, microarray-driven approach to analyze gene expression changes in ventricular tissue from VAChT KDHOM mice. We demonstrate that a decrease in cholinergic tone is associated with alterations in gene expression …

The Role Of Argininosuccinate Synthase Serine 328 Phosphorylation In Nitric Oxide Production, Ricci Haines

USF Tampa Graduate Theses and Dissertations

Until recently, the main mechanism of argininosuccinate synthase (AS) regulation was described to exist mainly at the level of transcription. Transcriptional regulation of AS has been shown to be coordinate with eNOS in response to shear stress, hypoxia, tumor necrosis factor á (TNF-á), and PPAR ã agonist troglitizone. However, it is now understood that one level of NO regulation is cellular control of arginine availability to eNOS via post-translational modifications of AS such as phosphorylation. The purpose of this investigation was to determine under what conditions AS is phosphorylated at S328, identify the pathway that AS phosphorylation at S328 plays …