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Regulated Expression of Genes/Proteins Critical to Anionic Amino Acid N Metabolism by Developing and Aging Beef Cattle
J.C. Matthews, J.A. Boling
Department of Animal and Food Sciences
The anionic amino acids aspartate and glutamate are critical for, and extensively metabolized to support, whole-animal energy and N metabolism in ruminants. The overall hypothesis being tested in this project is that expression of membrane transporters and metabolizing enzymes of glutamate and aspartate is sensitive to stage of life cycle and subtherapeutic levels of chlortetracycline.
2010 Project Description
The overall goal of this project is to optimize the dietary protein load to absorption and metabolic capacities of gastrointestinal and peripheral tissues throughout the life cycle of beef cattle, by developing the means to manipulate amino acid N metabolic capacity. Significant progress has been made this year towards meeting research goals of Objectives 1 and 2 of this project by discovering that glutamatergic neuron transmission and hepatic transcriptome likely are impaired in cattle consuming endophyte-infected tall fescue (the typical forage used in Kentucky's cow-calf industry).
Important activities included the conductance and mentoring of 1 Ph.D., 1 M.S., and 2 undergraduate student research projects involving anionic amino acid metabolism, and 1 Ph.D. project with aging cattle. Important events included (1) presentation of an invited Main Talk entitled "Alteration of Bovine Gene Expression and Protein Function by Ergot Alkaloids" at the Fescue Toxicosis session of the International Symposium on Fungal Endophytes of Grasses (ISFEG), August 28, 2010, as part of the 2010 Joint Meeting of the Mycological Society of America and the International Symposium on Fungal Endophytes of Grasses, Lexington, Kentucky, June 28-July 1, 2010, and (2) presentation of research results and their interpretation in a talk ("Egropeptines Inhibit Proteins Responsible for Bovine Neuronal Function") to over 80 Kentucky and Tennessee producers, commercial vendors, and extension agents at the 2010 Beef Bash, University of Kentucky Research and Education Center, Princeton, KY, September 23, 2010.
Important projects products were (1) release of the 19-microarray database (Gene Expression Omnibus, GSE23894, accepted August 31, 2010 and scheduled for release November 30, 2010), associated with "Hepatic Gene Expression Profiles of Growing Beef Steers Grazing High versus low Endophyte-infected Tall Fescue Grass", and (2) the Ph.D. dissertation "The Role of Glutamate Transport and Metabolism in Two Chronic Syndromes of Ruminants: Metabolic Acidosis and Fescue Toxicosis"(Yan Xue, 2010, University of Kentucky, Lexington; advisor, J. C. Matthews).
Study 1: using a grazing model, growing steers exposed to a summer-long (≥ 89 days) grazing of a high toxic endophyte (HE; 0.746 ug/g ergot alkaloids) tall fescue pasture (n=10) vs a low toxic endophyte (LE; 0.023 ug/g ergot alkaloids) tall fescue-mixed grass pasture (n=9) displayed classic phenotypic and clinical characteristics of fescue toxicosis, including decreased average daily gain, serum alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase. Concomitantly, immunoblot analysis found that hepatic contents of aspartate aminotransferase and cytosolic phosphoenolpyruvate carboxykinase were higher in HE steers. Microarray analysis of the same liver samples revealed increased (P≤0.01) expression of genes for proteins involved in mitochondrial shunting of aspartate carbons into pyruvate (alanine aminotransferase 2), and ATP (oxidative phosphorylation pathway) synthesis and glutamate into proline synthesis.
In Study 2, functional analysis of glutamate uptake by vesicular glutamate transporters (VGLUT) using neuronal synaptic vesicles isolated from mature steer cerebral tissue synaptic vesicles revealed that four naturally-occurring ergopeptines in endophyte-infected tall fescue are potent inhibitors of VGLUT activity, including a non-competitive mechanism of action by ergovaline. Thus, the findings of this research reveal the previously unknown interactions of ergot alkaloids with two anionic amino acid metabolic systems.
Because endophyte-infected tall fescue is the predominant feedstuff (about 35 million acres) of Kentucky and the greater forage-based cattle operations of the Eastern-Midwestern transition zone of U.S.A., these findings are relevant to the production of about 8 million beef cow-calf pairs in this region, including Kentucky's 1.2 million cow herd.
Matthews, J. C. 2010. Nutrient Transporters in Support of Ruminant Growth and Development: Novel and Updated Findings. J. Anim. Sci. Vol. 88, E-Suppl. 1, pg 270-271.
Liao, S. F., J. S. Monegue, M. D. Lindemann, G. L. Cromwell, and J. C. Matthews. 2010. Expression of Borate Transporter (NaBC1) mRNA by Growing Pigs is Sensitive to Dietary Boron Levels. J. Anim. Sci. Vol. 88, E-Suppl. 2, pg 662.
Liao, S. F., K. R. Brown, A. J. Stromberg, W. R. Burris, J. A. Boling, and J. C. Matthews. 2010. Dietary Supplementation of Selenium in Inorganic and Organic Forms Differentially and Commonly Alters Blood and Liver Selenium Concentrations and Liver Gene Expression Profiles of Growing Beef Heifers. Biological Trace Element Research published (April 13, 2010) first online as DOI: 10.1007/s12011-010-8685-2.
Taylor-Edwards, C. C., D. G. Burrin, J. C. Matthews, K. R. McLeoad, J. J. Holst, and D. L. Harmon. 2010. Expression of mRNA for Proglucagon and Glucagon-like Peptide-2 (GLP-2) Receptor in the Ruminant Gastrointestinal Tract and the Influence of Energy Intake. Domestic Animal Endocrinology, 39:181-193.
Brennan, K. M., W. R. Burris, J. A. Boling, and J. C. Matthews. 2010. Effects of Selenium Source on Blood Selenium Content, Blood Cell Counts and Peripheral Mononuclear Cell mRNA Profiles in Maturing Beef Heifers. FASEB J. 24:916.4.
Liao, S. F., K. R. Brown, A. J. Stromberg, W. R. Burris, J. A. Boling, and J. C. Matthews. 2010. Selenium Fed in Inorganic and Organic Forms Differentially and Commonly Alters Liver Gene Expression Profile of Growing Beef Heifers. J. Anim. Sci. Vol. 88, E-Suppl. 2, pg 513.
Xue, X., J. R. Strickland, J. A. Boling, J. C. Matthews. 2010. Ergovaline and Other Ergopeptine Alkaloids Inhibit Vesicular Glutamate Transporter (VGLUT)-mediated Activity of Bovine Synaptic Vesicles. J. Anim. Sci. Vol. 88, E-Suppl. 1, pg 679.
Slaughter, L. L., K. M. McClelland, S. F. Liao, K. M. Brennan, G. Rentfrow, J. A. Boling, and J. C. Matthews. 2010. Effects of Dietary Selenium on the Shelf-life Stability of Longissimus lumborum Steaks from Maturing Heifers. American Meat Science Association 62nd Reciprocal Meats Conference Lubbock, TX. Jun 20-23. Meeting Program & Abstracts: pp. 58-59
Matthews, J. C., Y. Xue, S. F. Liao, J. A. Boling. Alteration of Bovine Gene Expression and Protein Function by Ergot Alkaloids. 2010. 2010 Joint Meeting of the Mycological Society of America and the International Symposium on Fungal Endophytes of Grasses, Lexington, Kentucky, June 28-July 1, 2010.
Xue, Yan. 2010. The Role of Glutamate Transport and Metabolism in Two Chronic Syndromes of Ruminants: Metabolic Acidosis and Fescue Toxicosis. Ph.D. Dissertation, University of Kentucky, Lexington. Advisor: J. C. Matthews.