Protective role of alpha-actinin-3 in the response to an acute eccentric exercise bout.
The ACTN3 gene encodes for the alpha-actinin-3 protein, which has an important structural function in the Z line of the sarcomere in fast muscle fibers. A premature stop codon (R577X) polymorphism in the ACTN3 gene causes a complete loss of the protein in XX homozygotes. This study investigates a possible role for the alpha-actinin-3 protein in protecting the fast fiber from eccentric damage and studies repair mechanisms after a single eccentric exercise bout. Nineteen healthy young men (10 XX, 9 RR) performed 4 series of 20 maximal eccentric knee extensions with both legs. Blood (creatine kinase; CK) and muscle biopsy samples were taken to study differential expression of several anabolic (MyoD1, myogenin, MRF4, Myf5, IGF-1), catabolic (myostatin, MAFbx, and MURF-1), and contraction-induced muscle damage marker genes [cysteine- and glycine-rich protein 3 (CSRP3), CARP, HSP70, and IL-6] as well as a calcineurin signaling pathway marker (RCAN1). Baseline mRNA content of CSRP3 and MyoD1 was 49 + or - 12 and 67 + or - 25% higher in the XX compared with the RR group (P = 0.01-0.045). However, satellite cell number was not different between XX and RR individuals. After eccentric exercise, XX individuals tended to have higher serum CK activity (P = 0.10) and had higher pain scores than RR individuals. However, CSRP3 (P = 0.058) and MyoD1 (P = 0.08) mRNA expression tended to be higher after training in RR individuals compared with XX alpha-actinin-3-deficient subjects. This study suggests a protective role of alpha-actinin-3 protein in muscle damage after eccentric training and an improved stress-sensor signaling, although effects are small.
Research Center for Exercise and Health, Department of Biomedical Kinesiology, Faculty of Kinesiology and Rehabilitation Sciences, Katholieke Universiteit Leuven, Leuven.
Barbara
B
Vincent
An
A
Windelinckx
Henri
H
Nielens
Monique
M
Ramaekers
Marc
M
Van Leemputte
Peter
P
Hespel
Martine A
MA
Thomis
D000185:Actinin / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D003402:Creatine Kinase / Q000097:blood; D019610:Cytoprotection; D004268:DNA-Binding Proteins; D015444:Exercise; D005786:Gene Expression Regulation; D006720:Homozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D009119:Muscle Contraction / Q000235:genetics; D018763:Muscle Fatigue; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism / Q000473:pathology; D009124:Muscle Proteins / Q000235:genetics; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D010146:Pain / Q000378:metabolism / Q000473:pathology; D010147:Pain Measurement; D010641:Phenotype; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D055815:Young Adult
C118456:ACTN3 protein, human; D015415:Biomarkers; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; C108612:RCAN1 protein, human; D012333:RNA, Messenger; D000185:Actinin; D003402:Creatine Kinase