Vincent Barbara, Windelinckx An, Nielens Henri, Ramaekers Monique, Van Leemputte Marc, Hespel Peter, Thomis Martine A
Research Center for Exercise and Health, Department of Biomedical Kinesiology, Faculty of Kinesiology and Rehabilitation Sciences, Katholieke Universiteit Leuven, Leuven.
J Appl Physiol (1985). 2010 Aug;109(2):564-73. doi: 10.1152/japplphysiol.01007.2009. Epub 2010 May 27.
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.
α-辅肌动蛋白-3基因编码α-辅肌动蛋白-3蛋白，该蛋白在快肌纤维肌节的Z线中具有重要的结构功能。α-辅肌动蛋白-3基因中的一个提前终止密码子（R577X）多态性导致XX纯合子中该蛋白完全缺失。本研究调查了α-辅肌动蛋白-3蛋白在保护快肌纤维免受离心损伤方面的可能作用，并研究了单次离心运动后修复机制。19名健康年轻男性（10名XX型，9名RR型）双腿进行4组，每组20次最大离心膝关节伸展运动。采集血液（肌酸激酶；CK）和肌肉活检样本，以研究几种合成代谢（肌分化抗原1、生肌调节因子、肌肉调节因子4、肌因子5、胰岛素样生长因子-1）、分解代谢（肌肉生长抑制素、肌肉萎缩相关基因、肌肉泛素连接酶-1）和收缩诱导的肌肉损伤标记基因[富含半胱氨酸和甘氨酸的蛋白3、富含半胱氨酸的肌肉蛋白、热休克蛋白70和白细胞介素-6]以及钙调神经磷酸酶信号通路标记物（核因子活化的钙调神经磷酸酶1）的差异表达。与RR组相比，XX组中富含半胱氨酸的肌肉蛋白3和肌分化抗原1的基线mRNA含量分别高49±12%和67±25%（P = 0.01 - 0.045）。然而，XX型和RR型个体之间的卫星细胞数量没有差异。离心运动后，XX型个体的血清CK活性往往较高（P = 0.10），且疼痛评分高于RR型个体。然而，与缺乏α-辅肌动蛋白-3的XX型受试者相比，RR型个体训练后富含半胱氨酸的肌肉蛋白3（P = 0.058）和肌分化抗原1（P = 0.08）的mRNA表达往往更高。本研究表明，α-辅肌动蛋白-3蛋白在离心训练后对肌肉损伤具有保护作用，并能改善应激传感器信号传导，尽管作用较小。
