Journal of Applied Physiology vol:109 issue:2 pages:564-573
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 pre-mature 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 (CSRP3, CARP, HSP70, IL-6) as well as a calcineurin signaling pathway marker (RCAN1). Baseline mRNA content of CSRP3 and MyoD1 was 49+/-12% and 67+/-25% higher in the XX group compared to RR (p=0.01-0.045). However, satellite cell number was not different between XX or RR individuals. Following 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 t higher after training in RR individuals compared to 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.