TY - JOUR
T1 - Proteasome production in human muscle during nutritional inhibition of myofibrillar protein degradation
AU - Brodsky, Irwin G.
AU - Suzara, Dennis
AU - Furman, Mikhail
AU - Goldspink, Paul
AU - Ford, G. Charles
AU - Nair, K. Sreekumaran
AU - Kukowski, Jayme
AU - Bedno, Sheryl
N1 - Funding Information:
Supported by National Institutes of Health (NIH) Grant No. R29 DK 48998 awarded to I.G.B., General Clinical Research Center grants NIH Grant No. M01 RR13987 (University of Illinois at Chicago), and NIH M01 RR00585 (Mayo Clinic).
PY - 2004/3
Y1 - 2004/3
N2 - Protein undernutrition inhibits adenosine triphosphate (ATP)-dependent muscle protein degradation-a hallmark of the proteasome system. Here we report decreased myofibrillar protein degradation during dietary protein restriction without a concomitant decrease in proteasome gene expression, proteasome protein abundance, or proteasome in vivo fractional synthesis rate. Healthy human subjects consuming the average minimum adult protein requirement (0.71 g · kg-1 fat-free mass · d-1) exhibited substantially lower (68%) excretion of 3-methylhistidine, an indicator of myofibrillar protein breakdown, when compared with subjects consuming an ample, American-style protein intake (1.67 g · kg-1 fat-free mass · d-1). However, they displayed no difference in the expression of mRNA for proteasome subunits C2 or C3, in the content of C2 protein, or in the rate of incorporation of stable isotopically labeled L-[1-13C]-leucine into proteasome proteins. The results demonstrate that nutritional inhibition of myofibrillar protein degradation does not involve suppression in vivo of proteasome production in man. This suggests that other elements of the ubiquitin-proteasome system, such as ubiquitination pathways, are more important than proteasome abundance in the nutritional regulation of skeletal muscle mass.
AB - Protein undernutrition inhibits adenosine triphosphate (ATP)-dependent muscle protein degradation-a hallmark of the proteasome system. Here we report decreased myofibrillar protein degradation during dietary protein restriction without a concomitant decrease in proteasome gene expression, proteasome protein abundance, or proteasome in vivo fractional synthesis rate. Healthy human subjects consuming the average minimum adult protein requirement (0.71 g · kg-1 fat-free mass · d-1) exhibited substantially lower (68%) excretion of 3-methylhistidine, an indicator of myofibrillar protein breakdown, when compared with subjects consuming an ample, American-style protein intake (1.67 g · kg-1 fat-free mass · d-1). However, they displayed no difference in the expression of mRNA for proteasome subunits C2 or C3, in the content of C2 protein, or in the rate of incorporation of stable isotopically labeled L-[1-13C]-leucine into proteasome proteins. The results demonstrate that nutritional inhibition of myofibrillar protein degradation does not involve suppression in vivo of proteasome production in man. This suggests that other elements of the ubiquitin-proteasome system, such as ubiquitination pathways, are more important than proteasome abundance in the nutritional regulation of skeletal muscle mass.
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U2 - 10.1016/j.metabol.2003.10.015
DO - 10.1016/j.metabol.2003.10.015
M3 - Article
C2 - 15015147
AN - SCOPUS:2542438679
SN - 0026-0495
VL - 53
SP - 340
EP - 347
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 3
ER -