title: Cumulative 3-nitrotyrosine in specific muscle proteins is associated with muscle loss during aging.
abstract: Post-translational oxidative protein modifications which are more marked during aging and/or high-calorie (HC) diets affect protein function and metabolism. Protein function and metabolism are different according to the type of muscle proteins. Oxidative muscle protein modifications may thus be associated with age-related sarcopenia, and HC may be implicated in the development of sarcopenia by emphasizing protein modifications. Understanding the role of protein modifications in the process of sarcopenia and metabolism associated with a high fat diet may be elucidated by investigations with skeletal muscle protein subfractionations. To study this hypothesis, carbonylated protein (CP) and 3-nitrotyrosine (3-NT) levels were measured in mixed, sarcoplasmic, myofibrillar and mitochondrial protein fractions of quadriceps in rats aged 6months (A) and 25months (O) fed a normal calorie (NC) or HC diet for 3months (AN, AH, ON, OH n=7-8). Muscle weight was lower in the older rats (AN: 0.79±0.03g, ON: 0.43±0.12g, P<0.05), but no HC effect was observed. CP did not differ between groups while 3-NT accumulated significantly in ON compared with AN, especially in mitochondria (2.4±0.5, 1.3±0.1, 1.9±0.4, 2.9±1.2 -fold in mixed, sarcoplasmic, myofibrillar and mitochondrial fractions respectively, P<0.05). 3-NT in mixed protein was negatively correlated with muscle mass (r(2)=-0.812). 3-NT accumulation during HC was observed only in specific proteins of mitochondria (100kDa) (1.0±0.6, 1.7±0.9, 3.3±1.4 and 7.0±2.5 -fold in AN, AH, ON and OH, respectively, P<0.05). Hence cumulative 3-NT in skeletal muscle protein appears associated with the development of age-related muscle loss. Mitochondrial proteins are more prone to nitration during aging and nutritional stress.
authors: INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand, France.
authors: Hitoshi
authors: H
authors: Murakami
authors: Christelle
authors: C
authors: Guillet
authors: Nicolas
authors: N
authors: Tardif
authors: Jerome
authors: J
authors: Salles
authors: Carole
authors: C
authors: Migné
authors: Yves
authors: Y
authors: Boirie
authors: Stephane
authors: S
authors: Walrand
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001835:Body Weight; D002149:Energy Intake; D006614:Hindlimb; D008931:Mitochondria, Muscle / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D009210:Myofibrils / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D050050:Protein Carbonylation; D052097:Quadriceps Muscle / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D055948:Sarcopenia / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; C002744:3-nitrotyrosine; D014443:Tyrosine