A leucine‐supplemented diet restores the defective postprandial inhibition of proteasome‐dependent proteolysis in aged rat skeletal muscle

L Combaret, D Dardevet, I Rieu… - The Journal of …, 2005 - Wiley Online Library
L Combaret, D Dardevet, I Rieu, MN Pouch, D Béchet, D Taillandier, J Grizard, D Attaix
The Journal of physiology, 2005Wiley Online Library
We tested the hypothesis that skeletal muscle ubiquitin–proteasome‐dependent proteolysis
is dysregulated in ageing in response to feeding. In Experiment 1 we measured rates of
proteasome‐dependent proteolysis in incubated muscles from 8‐and 22‐month‐old rats,
proteasome activities, and rates of ubiquitination, in the postprandial and postabsorptive
states. Peptidase activities of the proteasome decreased in the postabsorptive state in 22‐
month‐old rats compared with 8‐month‐old animals, while the rate of ubiquitination was not …
We tested the hypothesis that skeletal muscle ubiquitin–proteasome‐dependent proteolysis is dysregulated in ageing in response to feeding. In Experiment 1 we measured rates of proteasome‐dependent proteolysis in incubated muscles from 8‐ and 22‐month‐old rats, proteasome activities, and rates of ubiquitination, in the postprandial and postabsorptive states. Peptidase activities of the proteasome decreased in the postabsorptive state in 22‐month‐old rats compared with 8‐month‐old animals, while the rate of ubiquitination was not altered. Furthermore, the down‐regulation of in vitro proteasome‐dependent proteolysis that prevailed in the postprandial state in 8‐month‐old rats was defective in 22‐month‐old rats. Next, we tested the hypothesis that the ingestion of a 5% leucine‐supplemented diet may correct this defect. Leucine supplementation restored the postprandial inhibition of in vitro proteasome‐dependent proteolysis in 22‐month‐old animals, by down‐regulating both rates of ubiquitination and proteasome activities. In Experiment 2, we verified that dietary leucine supplementation had long‐lasting effects by comparing 8‐ and 22‐month‐old rats that were fed either a leucine‐supplemented diet or an alanine‐supplemented diet for 10 days. The inhibited in vitro proteolysis was maintained in the postprandial state in the 22‐month‐old rats fed the leucine‐supplemented diet. Moreover, elevated mRNA levels for ubiquitin, 14‐kDa ubiquitin‐conjugating enzyme E2, and C2 and X subunits of the 20S proteasome that were characteristic of aged muscle were totally suppressed in 22‐month‐old animals chronically fed the leucine‐supplemented diet, demonstrating an in vivo effect. Thus the defective postprandial down‐regulation of in vitro proteasome‐dependent proteolysis in 22‐month‐old rats was restored in animals chronically fed a leucine‐supplemented diet.
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