Chronic metabolic acidosis increases mRNA levels for components of the ubiquitin-mediated proteolytic pathway in skeletal muscle of dairy cows.
Ruminants fed high-grain diets often are subjected to ruminal acidosis, which can lead to excessive absorption of lactate into the blood stream, thereby causing metabolic acidosis. Metabolic acidosis leads to body protein loss, mainly due to increased skeletal muscle degradation. Our objective was to determine the effects of metabolic acidosis on the messenger RNA (mRNA) abundance of genes encoding components of the ubiquitin-mediated proteolytic pathway in the skeletal muscle of lactating Holstein cows. Cows (n = 20) were assigned to one of two treatments: 1) control; or 2) NutriChlor 18-8, an HCl-treated supplement, which was fed to induce chronic metabolic acidosis. The longissimus muscle was biopsied before and after 10 d of treatments. Total RNA isolated from muscle tissue was hybridized with (32)P-labeled cDNA probes encoding for 14-kDa ubiquitin carrier protein E2 (14-kDa E2), ubiquitin, and C8 and C9 subunits of the 20S proteasome. Induction of metabolic acidosis increased (P < 0.05) skeletal muscle mRNA levels for ubiquitin (25%), 14-kDa E2 (34%), and the C8 subunit (20%); however, mRNA abundance for the C9 subunit was unaffected (P > 0.05). These results suggest that up-regulation of the ubiquitin-proteasome pathway is the mechanism by which metabolic acidosis stimulates muscle wasting in ruminants.
Mutsvangwa
Timothy
T
Department of Animal and Poultry Science, University of Guelph, Guelph, ON, Canada N1G 2W1.
Gilmore
James
J
Squires
James E
JE
Lindinger
Michael I
MI
McBride
Brian W
BW
D000138:Acidosis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001639:Bicarbonates / Q000097:blood; D002417:Cattle; D003546:Cysteine Endopeptidases / Q000235:genetics*; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D003612:Dairying; D019587:Dietary Supplements; D005260:Female; D006851:Hydrochloric Acid / Q000008:administration & dosage / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D009097:Multienzyme Complexes / Q000235:genetics*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000378:metabolism*; D025801:Ubiquitin / Q000235:genetics*; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics
D001639:Bicarbonates; D017931:DNA Primers; D018076:DNA, Complementary; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D025801:Ubiquitin; C046288:ubiquitin carrier proteins; D044763:Ubiquitin-Conjugating Enzymes; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D006851:Hydrochloric Acid