Influence of glutamine infusion on ubiquitin, caspase-3, cathepsins L and B, and m-calpain expression in sheep with nutritionally induced metabolic acidosis

• Published in: Journal of animal science 2009-06, Vol.87 (6), p.2073-2079
• Main Authors: Greenwood, S.L, AlZahal, O, Swanson, K.C, Matthews, J.C, McBride, B.W
• Format: Article
• Language: English
• Subjects: Acid-Base Equilibrium - drug effects; acidosis; Acidosis - chemically induced; Amino Acids - blood; Animal Feed; Animal Nutritional Physiological Phenomena; animal tissues; Animals; biomarkers; calpain; Calpain - genetics; Calpain - metabolism; Caspase 3 - genetics; Caspase 3 - metabolism; caspase-3; cathepsin B; Cathepsin B - genetics; Cathepsin B - metabolism; Cathepsin L; cathepsins; Cathepsins - genetics; Cathepsins - metabolism; Cysteine Endopeptidases - genetics; Cysteine Endopeptidases - metabolism; Diet - veterinary; dietary supplements; gene expression; Gene Expression Regulation - drug effects; glutamine; Glutamine - administration & dosage; Glutamine - pharmacology; m-calpain; messenger RNA; physiological regulation; protein degradation; protein synthesis; proteolysis; randomized clinical trials; sheep; Sheep - physiology; sheep diseases; Sheep Diseases - chemically induced; ubiquitin; Ubiquitin - genetics; Ubiquitin - metabolism
• ISSN: 0021-8812; 1525-3163
• DOI: 10.2527/jas.2008-1748

Provision of AA has shown success in attenuating proteolytic activity in monogastrics suffering from metabolic acidosis. However, it is unknown whether AA supplementation can provide any beneficial effects to ruminants with nutritionally induced metabolic acidosis. The objective of the current study was to examine the effects of glutamine infusion on various protein degradation components across several tissues in sheep with induced metabolic acidosis. Sheep were assigned to a randomized complete block design with 2 x 2 factorial arrangement of treatments (n = 6 sheep/treatment) consisting of a control or acidosis diet, and receiving a saline or L-glutamine infusion. Sheep were fed diets for 10 d and slaughtered on d 11. Liver, kidney, and muscle samples were collected at slaughter and examined for relative messenger RNA (mRNA) expression of ubiquitin, C8, E2, cathepsin L, cathepsin B, caspase-3, and m-calpain, as well as protein expression of ubiquitin. Relative mRNA expression of C8 (P = 0.02), E2 (P = 0.06), and ubiquitin (P = 0.07) was less in kidney in acidotic vs. control sheep. Additionally, mRNA expression of m-calpain in kidney was greater (P = 0.01) as a result of glutamine infusion. There were no significant alterations (P > 0.10) in mRNA of any component as a result of acidosis in the liver or muscle. This study demonstrates the inability of metabolic acidosis to increase expression of the ubiquitin-mediated proteolytic pathway in skeletal muscle; however, downregulation of renal mRNA expression of these components is apparent during the induction of metabolic acidosis.