Protective role of α-actinin-3 in the response to an acute eccentric exercise bout

• Published in: Journal of applied physiology (1985) 2010-08, Vol.109 (2), p.564-573
• Main Authors: VINCENT, Barbara, WINDELINCKX, An, NIELENS, Henri, RAMAEKERS, Monique, VAN LEEMPUTTE, Marc, HESPEL, Peter, THOMIS, Martine A
• Format: Article
• Language: English
• Subjects: Actinin - genetics; Actinin - metabolism; Biological and medical sciences; Biomarkers - blood; Biopsy; Creatine Kinase - blood; Cytoprotection; Exercise; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Homozygote; Humans; Intracellular Signaling Peptides and Proteins - genetics; Male; Muscle Contraction - genetics; Muscle Fatigue; Muscle Fibers, Fast-Twitch - metabolism; Muscle Fibers, Fast-Twitch - pathology; Muscle Proteins - genetics; Muscle Strength; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Pain - metabolism; Pain - pathology; Pain Measurement; Phenotype; Polymorphism, Genetic; RNA, Messenger - metabolism; Satellite Cells, Skeletal Muscle - metabolism; Satellite Cells, Skeletal Muscle - pathology; Time Factors; Young Adult
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.01007.2009

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.