Chronic contractile activity upregulates the proteasome system in rabbit skeletal muscle.
Remodeling of skeletal muscle in response to altered patterns of contractile activity is achieved, in part, by the regulated degradation of cellular proteins. The ubiquitin-proteasome system is a dominant pathway for protein degradation in eukaryotic cells. To test the role of this pathway in contraction-induced remodeling of skeletal muscle, we used a well-established model of continuous motor nerve stimulation to activate tibialis anterior (TA) muscles of New Zealand White rabbits for periods up to 28 days. Western blot analysis revealed marked and coordinated increases in protein levels of the 20S proteasome and two of its regulatory proteins, PA700 and PA28. mRNA of a representative proteasome subunit also increased coordinately in contracting muscles. Chronic contractile activity of TA also increased total proteasome activity in extracts, as measured by the hydrolysis of a proteasome-specific peptide substrate, and the total capacity of the ubiquitin-proteasome pathway, as measured by the ATP-dependent hydrolysis of an exogenous protein substrate. These results support the potential role of the ubiquitin-proteasome pathway of protein degradation in the contraction-induced remodeling of skeletal muscle.
Ordway
G A
GA
Department of Physiology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235-9040, USA. gordwa@mednet.swmed.edu
Neufer
P D
PD
Chin
E R
ER
DeMartino
G N
GN
D000818:Animals; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004558:Electric Stimulation; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000502:physiology; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D014452:Ubiquitins / Q000378:metabolism; D015854:Up-Regulation
D009097:Multienzyme Complexes; D009124:Muscle Proteins; D012333:RNA, Messenger; D014452:Ubiquitins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex