Cellular and Molecular Physiology Commons^™

Ablation Of Matrix Metalloproteinase-9 Prevents Cardiomyocytes Contractile Dysfunction In Diabetics., Priyanka Prathipati, Naira Metreveli, Shyam Sundar Nandi, Suresh C. Tyagi, Paras K. Mishra

Journal Articles: Cellular & Integrative Physiology

Elevated expression and activity of matrix metalloproteinase-9 (MMP9) and decreased contractility of cardiomyocytes are documented in diabetic hearts. However, it is unclear whether MMP is involved in the regulation of contractility of cardiomyocytes in diabetic hearts. In the present study, we tested the hypothesis that MMP9 regulates contractility of cardiomyocytes in diabetic hearts, and ablation of MMP9 prevents impaired contractility of cardiomyocytes in diabetic hearts. To determine the specific role of MMP9 in cardiomyocyte contractility, we used 12-14 week male WT (normoglycemic sibling of Akita), Akita, and Ins(2+∕-)/MMP9(-∕-) (DKO) mice. DKO mice were generated by cross-breeding male Ins2(+∕-) Akita (T1D) …

Hoxd Expression In The Fin-Fold Compartment Of Basal Gnathostomes And Implications For Paired Appendage Evolution, Frank J. Tulenko, Gaius J. Augustus, James L. Massey, Seth E. Sims

Faculty Articles

The role of Homeobox transcription factors during fin and limb development have been the focus of recent work investigating the evolutionary origin of limb-specific morphologies. Here we characterize the expression of HoxD genes, as well as the cluster-associated genes Evx2 and LNP, in the paddlefish Polyodon spathula, a basal ray-finned fish. Our results demonstrate a collinear pattern of nesting in early fin buds that includes HoxD14, a gene previously thought to be isolated from global Hoxregulation. We also show that in both Polyodon and the catsharkScyliorhinus canicula (a representative chondrichthyan) late phaseHoxD transcripts are present in cells of the fin-fold …

Single Nucleotide Polymorphisms In Cldn14 And Smoc1 Affecting Bone Mineral Density Influence Other Musculoskeletal Traits, Christopher Payette, Courtney Sprouse, Cara Goerlich, Heather A. Gordish-Dressman, Thomas Lynch, Heather Flynn, Leticia M. Ryan, Eric P. Hoffman, Monica J. Hubal, Paul D. Thompson, Theodore J. Angelopoulos, Paul M. Gordon, Niall M. Moyna, Linda S. Pescatello, Paul S. Visich, Robert F. Zoeller, Laura L. Tosi

GW Research Days 2016 - 2020

Background: A recent genome-wide association study (GWAS) identified novel genes influencing bone mineral density (BMD). This three stage GWAS identified two novel loci: rs227425 in the SPARC-Related Modular Calcium Binding 1 gene (SMOC1) was significantly associated with BMD and rs170183 in the claudin 14 (CLDN14) gene was significantly associated with BMD in females.

Objective: The purpose of this study was to determine if two novel single nucleotide polymorphisms (SNPs) known to affect BMD are associated with other musculoskeletal traits.

Methods/Design :The Bone Health Cohort consists of 150 African-American participants enrolled at Children’s National Health System as part of …

Efn-4 Functions In Lad-2-Mediated Axon Guidance In Caenorhabditis Elegans, Alicia A. Schwieterman, Cory J. Donelson, Jonathan L. Mcmurry, Martin L. Hudson

Faculty Articles

During development of the nervous system, growing axons rely on guidance molecules to direct axon pathfinding. A well-characterized family of guidance molecules are the membrane-associated ephrins, which together with their cognate Eph receptors, direct axon navigation in a contact-mediated fashion. InC. elegans, the ephrin-Eph signaling system is conserved and is best characterized for their roles in neuroblast migration during early embryogenesis. This study demonstrates a role for theC. elegansephrin EFN-4 in axon guidance. We provide both genetic and biochemical evidence that is consistent with theC. elegansdivergent L1 cell adhesion molecule LAD-2 acting as a non-canonical ephrin receptor to EFN-4 to …

Isothermal Titration Calorimetry Uncovers Substrate Promiscuity Of Bicupin Oxalate Oxidase From Ceriporiopsis Subvermispora, Hassan Rana, Patricia Moussatche, Lis Souza Rocha, Ellen W. Moomaw

Faculty Articles

Isothermal titration calorimetry (ITC) may be used to determine the kinetic parameters of enzymecatalyzed reactions when neither products nor reactants are spectrophotometrically visible and when the reaction products are unknown. We report here the use of the multiple injection method of ITC to characterize the catalytic properties of oxalate oxidase (OxOx) from Ceriporiopsis subvermispora (CsOxOx), a manganese dependent enzyme that catalyzes the oxygen-dependent oxidation of oxalate to carbon dioxide in a reaction coupled with the formation of hydrogen peroxide. CsOxOx is the first bicupin enzyme identified that catalyzes this reaction. The multiple injection ITC method of measuring OxOx activity involves …

Gene Expression Microarray Data From Human Microvascular Endothelial Cells Supplemented With A Low Concentration Of Niacin, Nica M. Borradaile, Jennifer M. Hughes-Large

Physiology and Pharmacology Publications

The systemic lipid modifying drug, niacin, can directly improve human microvascular endothelial cell angiogenic function under lipotoxic conditions, possibly through activation of niacin receptors [1]. Here we provide accompanying data collected using Affymetrix GeneChip microarrays to identify changes in gene expression in human microvascular endothelial cells treated with 10 μM niacin. Statistical analyses of robust multi-array average (RMA) values revealed that only 16 genes exhibited greater than 1.3-fold differential expression. Of these 16, only 5 were identified protein coding genes, while 3 of the remaining 11 genes appeared to be small nuclear/nucleolar RNAs. Altered expression of EFCAB4B, …

Low-Dose Aronia Melanocarpa Concentrate Attenuates Paraquat-Induced Neurotoxicity., Adam J. Case, D Agraz, Iman M. Ahmad, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Herbicides containing paraquat may contribute to the pathogenesis of neurodegenerative disorders such as Parkinson's disease. Paraquat induces reactive oxygen species-mediated apoptosis in neurons, which is a primary mechanism behind its toxicity. We sought to test the effectiveness of a commercially available polyphenol-rich Aronia melanocarpa (aronia berry) concentrate in the amelioration of paraquat-induced neurotoxicity. Considering the abundance of antioxidants in aronia berries, we hypothesized that aronia berry concentrate attenuates the paraquat-induced increase in reactive oxygen species and protects against paraquat-mediated neuronal cell death. Using a neuronal cell culture model, we observed that low doses of aronia berry concentrate protected against paraquat-mediated …

Angiotensin Ii-Induced Hypertension Is Attenuated By Overexpressing Copper/Zinc Superoxide Dismutase In The Brain Organum Vasculosum Of The Lamina Terminalis., John P. Collister, Heather Taylor-Smith, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Angiotensin II (AngII) can access the brain via circumventricular organs (CVOs), including the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), to modulate blood pressure. Previous studies have demonstrated a role for both the SFO and OVLT in the hypertensive response to chronic AngII, yet it is unclear which intracellular signaling pathways are involved in this response. Overexpression of copper/zinc superoxide dismutase (CuZnSOD) in the SFO has been shown to attenuate the chronic hypertensive effects of AngII. Presently, we tested the hypothesis that elevated levels of superoxide (O2 (∙-)) in the OVLT contribute to the hypertensive effects …

Low-Dose Aronia Melanocarpa Concentrate Attenuates Paraquat-Induced Neurotoxicity, Adam J. Case, Daniel Agraz, Iman M. Ahmad, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

No abstract provided.

Angiotensin Ii-Induced Hypertension Is Attenuated By Overexpressing Copper/Zinc Superoxide Dismutase In The Brain Organum Vasculosum Of The Lamina Terminalis., John P. Collister, Heather Taylor-Smith, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman

Journal Articles: Cellular & Integrative Physiology

Angiotensin II (AngII) can access the brain via circumventricular organs (CVOs), including the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), to modulate blood pressure. Previous studies have demonstrated a role for both the SFO and OVLT in the hypertensive response to chronic AngII, yet it is unclear which intracellular signaling pathways are involved in this response. Overexpression of copper/zinc superoxide dismutase (CuZnSOD) in the SFO has been shown to attenuate the chronic hypertensive effects of AngII. Presently, we tested the hypothesis that elevated levels of superoxide (O2 (∙-)) in the OVLT contribute to the hypertensive effects …

Calcitriol Increases Ceramide, Diacylglycerol, And Expression Of Genes Involved In Lipid Packaging In Skeletal Muscle, Grace Elizabeth Jefferson

Theses and Dissertations--Kinesiology and Health Promotion

Background: Vitamin D is crucial for skeletal muscle function. 25-hidroxyvitamin D (25(OH)D) has been correlated with skeletal muscle mass and intramyocellular lipid (IMCL) content. The purpose of this study was to understand how calcitriol, the active vitamin D metabolite, directly affects myocellular size and lipid partitioning.

Methods: C₂C₁₂ myotubes were treated with calcitriol (100nM) or vehicle control for 24 or 96 h. Myotube diameter and protein synthesis rate were measured to determine effects of calcitriol on myocellular size. Intramyocellular triacylglycerol (IMTG), diacylglycerol (DAG), and ceramide content were measured by LC/MS. Expression of genes involved in lipid packaging …

A Mechanistic Study Of An Ipsc Model For Leigh’S Disease Caused By Mtdna Mutataion (8993 T>G), John P. Galdun

Theses and Dissertations

Mitochondrial diseases encompass a broad range of devastating disorders that typically affect tissues with high-energy requirements. These disorders have been difficult to diagnose and research because of the complexity of mitochondrial genetics, and the large variability seen among patient populations. We have devised and carried out a mechanistic study to generate a cell based model for Leigh’s disease caused by mitochondrial DNA mutation 8993 T>G. Leigh’s disease is a multi-organ system disorder that depends heavily on the mutation burden seen within various tissues. Using new reprogramming and sequencing technologies, we were able to show that Leigh’s disease patient fibroblasts …

Ppap2b Expression Limits Lesion Formation In Murine Models Of Atherosclerosis, Paul A. Mueller

Theses and Dissertations--Physiology

Coronary artery disease (CAD) is the leading cause of death in both men and women worldwide and is defined as a narrowing of the coronary arteries due to accumulation of atherosclerotic plaques. Genome-wide association studies have identified risk loci within the gene PPAP2B that confers increased risk of developing CAD. Evidence suggests these aforementioned SNPs are regulating PPAP2B expression in a cis-manner through the interruption of transcription factor binding sites. PPAP2B encodes the lipid phosphate phosphatase 3 enzyme that plays a key role in degrading bioactive lysophosphatidic acid (LPA). LPA has a plethora of effects on vascular tissue and is …

Critical Role Of C-Jun N-Terminal Kinase Signaling In Binge Alcohol-Driven Atrial Arrhythmic Remodeling, Jiajie Yan Yan

Dissertations

Holiday Heart Syndrome (HHS) is cardiac arrhythmia induced by binge alcohol consumption, a drinking pattern affects 38 million adults in our society. Atrial fibrillation (AF) is the most frequently diagnosed arrhythmia in HHS and causes significant morbidity and mortality. Despite the intensive prevention effort nationwide, the binge drinking population keeps rising. However, no effective treatment strategies are available for binge drinking induced AF due to the unknown underlying mechanisms. In this thesis, I aim to elucidate the mechanisms of binge alcohol-promoted atrial arrhythmogenicity by using a mouse model of repeated binge alcohol exposure established in the Ai Lab.

The Ai …

High Affinity Block Of Icl,Swell By Thiol-Reactive Small Molecules, Sung H. Park

Theses and Dissertations

Ebselen (Ebs) is considered as a glutathione peroxidase (GPx) mimetic and primarily thought to function by scavenging intracellular reactive oxygen species (ROS). Previous to our work, Deng et al. (2010a) demonstrated complete block of I_Cl,swell with 15 microM Ebs following endothelin-1 (ET-1) induced activation of the current in cardiomyocytes. This block was presumed to take effect mainly via the quenching of ROS. Nonetheless, our work with DI TNC1 astrocytes strongly emphasizes that Ebs might function by an alternative mechanism based on its kinetic profile in blocking I_Cl,swell. Our experiments showed that 45 nM Ebs can fully block …

Changes In Brain Water Content In The Rainbow Trout (Oncorhynchus Mykiss) And In The Goldfish (Carassius Auratus) Due To High External Ammonia Exposure, Phillip Q.H. Pham-Ho

Theses and Dissertations (Comprehensive)

In fishes, hyperammonemia may occur following feeding or exposure to abnormally high concentrations of environmental ammonia due to sewage effluents, agricultural run-off and in crowded aquaculture pens. Increased internal ammonia can result in hyperactivity, convulsions, coma and death. In mammals, it is also associated with potentially fatal brain edema, in which the accumulation of intracellular water results in swelling, increased intracranical pressure and herniation leading to death. Recently it was shown that rainbow trout (Oncorhynchus mykiss) and goldfish (Carassius auratus) experience brain swelling following exposure to high external ammonia (HEA). However, the mechanism of ammonia-induced brain …

The Role Of Oxidative Stress In The Mechanisms Of Ammonia-Induced Brain Swelling And Tolerance In The Goldfish (Carassius Auratus), David F. Jones Lisser Mr.

Theses and Dissertations (Comprehensive)

Toxic build-ups of ammonia can cause potentially fatal brain swelling in mammals, but such swelling is reversible in the anoxia- and ammonia-tolerant goldfish (Carassius auratus). The mechanisms of ammonia-induced brain swelling and tolerance remain elusive, but several studies have suggested a role for reactive oxygen species (ROS), which may damage proteins and lipids in the plasma membrane of astrocytes in the brain. As a result, osmotic gradients across cell membranes may be altered leading to water uptake by astrocytes and swelling. While a role for ROS has been proposed in mammals, no studies have addressed this question in …

A Missing Link In The Ionoregulatory Strategy Of Larval Sea Lamprey (Petromyzon Marinus) And African Lungfish (Protopterus Annectens): A Closer Look Into The Role Of The Non-Gastric H+/K+-Atpase, Justine E. Doherty

Theses and Dissertations (Comprehensive)

Fishes living in freshwater need to actively compensate for the diffusive loss of ions and osmotic gain of water. The gill is the primary organ of ion regulation and contains an array of ion transport proteins to help maintain homeostasis. Two of the more well studied ion pumps are the Na⁺/K⁺-ATPase (NKA) and vacuolar type proton ATPase (V-ATPase). This thesis focuses on another ion pump known as the non-gastric H⁺/K⁺-ATPase (ngHKA). The ngHKA (gene: atp12a) has not been found in any of the teleost fishes, indicating loss from that lineage. In …

Functional Characterization Of A Novel Disaccharide Membrane Transporter In The Digestive Tract Of The American Lobster, Homarus Americanus, Olivia Scheffler

UNF Graduate Theses and Dissertations

In animals, the accepted model of carbohydrate digestion and absorption involves reduction of disaccharides into the simple sugars glucose, fructose and galactose. Previous studies have shown the presence of disaccharides maltose and trehalose in the blood of several crab species, the crayfish and the American lobster. In 2011, a gene for a distinct disaccharide sucrose transporter (SCRT) was first found in Drosophila melanogaster and characterized using a yeast expression system. The purpose of the current study was to identify and characterize a putative disaccharide transporter analog in crustaceans using the American lobster, Homarus americanus. Brush border membrane vesicles purified …

The Influence Of Abiotic Factors On The Uptake And Elimination Of 3-Trifluoromethyl-4-Nitrophenol By Larval Sea Lamprey (Petromyzon Marinus), Benjamin Livingston Hlina

Theses and Dissertations (Comprehensive)

The backbone of sea lamprey (Petromyzon marinus) control in the Great Lakes is the use of the piscicide, 3-trifluoromethyl-4-nitrophenol (TFM), which is applied to streams containing larval sea lampreys. However, TFM effectiveness can be influenced by abiotic factors such as pH and temperature, which fluctuate daily and seasonally. The objectives of this thesis were to evaluate the influence of pH, temperature, and season on the toxicity, uptake, and elimination of TFM by larval sea lamprey. Radio-labeled TFM (¹⁴C-TFM) was used to determine how TFM uptake rates varied at different water pHs or temperatures during exposure to …