title: Increase in levels of polyubiquitin and proteasome mRNA in skeletal muscle during starvation and denervation atrophy.
abstract: Most of the increased protein degradation in muscle atrophy caused by starvation and denervation is due to activation of a non-lysosomal ATP-dependent proteolytic process. To determine whether expression of the ubiquitin-proteasome-dependent pathway is activated in atrophying muscles, we measured the levels of mRNA for ubiquitin (Ub) and proteasome subunits, and Ub content. After rats had been deprived of food for 1 or 2 days, the concentration of the two polyubiquitin (polyUb) transcripts increased 2-4-fold in the pale extensor digitorum longus muscle and 1-2.5-fold in the red soleus, whereas total muscle RNA and total mRNA content fell by 50%. After denervation of the soleus, there was a progressive 2-3-fold increase in polyUb mRNA for 1-3 days, whereas total RNA content fell. On starvation or denervation, Ub concentration in the muscles also rose by 60-90%. During starvation, polyUb mRNA levels also increased in heart, but not in liver, kidney, spleen, fat, brain or testes. Although the polyUb gene is a heat-shock gene that is induced in muscles under certain stressful conditions, the muscles of starving rats or after denervation did not express other heat-shock genes. On starvation or denervation, mRNA for several proteasome subunits (C-1, C-3, C-5, C-8 and C-9) also increased 2-4-fold in the atrophying muscles. When the food-deprived animals were re-fed, levels of Ub and proteasome mRNA in their muscles returned to control values within 1 day. In contrast, no change occurred in the levels of muscle mRNAs encoding cathepsin L, cathepsin D and calpain 1 on denervation or food deprivation. Thus polyUb and proteasome mRNAs increased in atrophying muscles in co-ordination with activation of the ATP-dependent proteolytic process.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: R
authors.initials: R
authors.lastname: Medina
authors.forename: S S
authors.initials: SS
authors.lastname: Wing
authors.forename: A L
authors.initials: AL
authors.lastname: Goldberg
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001704:Biopolymers / Q000096:biosynthesis / Q000235:genetics*; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000235:genetics*; D010450:Endopeptidases / Q000378:metabolism; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D009097:Multienzyme Complexes / Q000096:biosynthesis / Q000235:genetics*; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000294:innervation* / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000209:etiology / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D025821:Polyubiquitin; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013217:Starvation / Q000378:metabolism*; D014452:Ubiquitins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D001704:Biopolymers; D006360:Heat-Shock Proteins; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D014452:Ubiquitins; D025821:Polyubiquitin; D000255:Adenosine Triphosphate; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex