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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.
2011 Project Description
Important project activities included the conductance and mentoring of 1 M.S., and 1 undergraduate student research projects involving anionic amino acid metabolism, and 1 Ph.D. project with aging cattle. Important events included presentation of beef cattle research results and their interpretation to over 120 Kentucky and Tennessee producers, commercial vendors, and extension agents at the 2011 University of Kentucky Field Day, July 21, Princeton, KY. Important projects products included publication of 6 research manuscripts and 4 abstracts, and an M.S. thesis.
Study 1: Using previously collected biological samples from growing steers exposed to a summer-long (≥ 89 days) grazing of either a high toxic endophyte (HE; 0.746 microgram/gram ergot alkaloids) tall fescue pasture (n=10) or a low toxic endophyte (LE; 0.023 microgram/gram ergot alkaloids) tall fescue-mixed grass pasture (n=9) (the model reported last year), we demonstrated that clinical and biochemical blood parameter response to grazing HE vs LE pastures could be divided into three groups:
- those that were continually altered (serum albumin, prolactin, cholesterol and RBC),
- those that were initially altered and then "recovered" (ADG, triglycerides, albumin/globulin ratio, Na, P, lymphocytes, and bilirubin), and
- those that developed after long-term exposure (LDH, AST, ALT, ALP, creatine kinase, glucose, monocytes, Ca, ammonia, and K).
The data from the trial also indicate that, with the exception of triglyceride concentrations, blood and clinical parameters are weakly correlated (if at all) to serum prolactin levels, the indicator of fescue toxicosis. Microarray analysis of liver samples after 36 days of grazing revealed increased (P≤0.01) expression of genes for proteins involved in mitochondrial ATP (oxidative phosphorylation pathway) synthesis vs LE steers, but unlike after 89 days (reported last year), no difference in genes responsible for proline or serine synthetic capacity. For the Longissimus dorsi, microarray profiling revealed a decreased protein synthetic capacity in HE vs LE steers after 36 days of grazing.
In Study 2, functional analysis of nucleoside uptake using an immortalized bovine renal cell culture model (MDBK cells) revealed that ergovaline (a predominant ergot alkaloid in endophyte-infected tall fescue inhibits an ubiquitously expressed nucleoside transporter (ENT1) activity, in a mechanism manner that is independent from the dopamine-like 2 receptor (which is thought to mediate much of ergovaline's pharmaceutical effects). Thus, consumption of ergovaline may impair body-wide nucleoside metabolism.
Thus, the findings of this research reveal the previously unknown interactions of ergot alkaloids with hepatic, skeletal muscle, and renal N-based 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.
Miles, E. D., Y. Xue, J. R. Strickland, J. A. Boling, and J. C. Matthews. 2011. Ergopeptines Bromocriptine and Ergovaline, and Domperidone, Inhibit Bovine Equilibrative Nucleoside Transporter 1-like Activity. Journal of Agriculture and Food Chemistry. 59:9691-9699.
Brennan, K. M., W. R. Burris, J. A. Boling and J. C. Matthews. 2011. Selenium Content in Blood Fractions and Liver of Beef Heifers is Greater with a Mix of Inorganic/Organic or Organic Versus Inorganic Supplemental Selenium Forms but the Time Required for Maximal Assimilation is Tissue-specific. Biological Trace Mineral Research. 144:504-516.
Xue, Y., J. R. Strickland, J. A. Boling, J. C. Matthews. 2011. Bovine Vesicular Glutamate Transporter Activity Is Inhibited by Ergovaline and Other Ergopeptines. Journal of Dairy Science 94:3331 - 3341.
Steele, M., G. Vandervoort, O. AlZahal, S. Hook, J. C. Matthews, and B. W. McBride. 2011. Rumen Epithelial Adaptation to High Grain Diets Involves the Coordinated Regulation of Genes Involved in Cholesterol Homeostasis. Physiological Genomics 43:308-316.
Strickland, J. R., M. L. Looper, J. C. Matthews, C. F. Rosenkrans, M. D. Flythe, and K. R. Brown. 2011. BOARD-INVITED REVIEW: St. Anthonys Fire in Livestock: Causes, Mechanisms and Potential Solution. Journal of Animal Science 89:1603-1626.
Liao, S. F., J. S. Monegue, M. D. Lindemann, G. L. Cromwell, and J. C. Matthews. 2010. Dietary Supplementation of Boron Differentially Affects Expression of Borate Transporter (NaBC1) mRNA by Jejunum and Kidney of Growing Pigs. Biological Trace Element Research, 143:901-912.
Brennan, K. M., J. A. Boling, R. Xiao, D. Mallonee, R. F. Power, and J. C. Matthews. 2011. Effects of Supplementation of Organic, Inorganic or a 50/50 Mix of Selenium on Gene Expression Profiles in the Longissmus Dorsi Muscle of Maturing Angus Beef Heifers. Journal of Animal Science, E-Suppl. 1, pg 110.
Joseph, P., G. Rentfrow, L. L. Slaughter, K. M. McClelland, S. P. Suman, J. A. Boling, K. M. Brennan, J. C. Matthews. 2011. Effect of Dietary Selenium Supplementation on Color Shelf-life of Beef Psoas major Steaks from Maturing Heifers. American Meat Science Association 64th Reciprocal Meat Conference, Kansas State University, June 19-22, 2011. Meeting Program & Abstracts: pg 45.
Matthews, J. C., D. C. Mahan, K. M. Brennan, S. F. Liao, W. R. Burris, and J. A. Boling. 2011. Mixed or Organic vs Inorganic Forms of Selenium (Se) Differentially Affect Tissue Se Concentrations of Growing Beef Heifers. J. Anim. Sci. Vol 89, E-Suppl. 2, Abstract no. 328.
Jackson, Joshua J. 2011. Duration of Grazing High Versus Low Endophyte (Neotyphodium coenophialum)-infected Tall Fescue by Growing Steers Differentially-Affects Blood Concentrations of Prolactin, Enzymes, and Metabolites. M.S. Thesis, University of Kentucky, Lexington. Advisor: J. C. Matthews.