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Effect Of Endurance Exercise And Resisitance Exercise On Wnt/β-catenin Signaling Pathway In PS1/PS2 Double Knockout Mice

Posted on:2016-01-07Degree:MasterType:Thesis
Country:ChinaCandidate:Y Y XuFull Text:PDF
GTID:2284330461975683Subject:Human Movement Science
Abstract/Summary:PDF Full Text Request
Overview:Skeletal muscle mass accounts for about half of total body weight, the function of contraction is essential to maintain stability and physical activity. In addition to as "power engine" of the body, but it also play a decisive role in the maintenance of the body homeostasis. After be damaged, Adult skeletal muscle has a strong repair or regeneration capacity, and the formation of a new myogenic fibers in the process of repair(or regeneration) mainly due to specialized muscle-derived stem cells-muscle satellite cells (SC, satellite cells) under the basement membrane of mature muscle fibers. There are two destination of activated SC:self-renewal and differentiation specificity. On one hand, SC restored silent state of self-renewal and other ways to maintain the satellite cell pool through asymmetric division, intramuscular other stem cells migrate into SC area and the proliferation of MPCs, avoiding depletion. On the other hand, activated SC formed new muscle fibers by forming a multi-core muscle tube, and then integrated with each other or fusion with neighboring muscle fibers. The balance between the maintenance of the satellite cell pool and skeletal muscle homeostasis has a crucial role. The activated SC proceed to self-renewal or differentiation depends on various factors intracellular transcriptional regulation, specialized niche secreted extracellular signal source. The study found that the canonical Wnt signaling pathway in the formation of new myogenic differentiation SC fiber plays an important role in the process. Currently, the research of effect of Exercise, especially different modes of exercise on the canonical Wnt signaling pathway, SC self-renewal and differentiation of skeletal muscle repair and regeneration process still less, and Presenilin (PS), as the "set point" in the coordination, dynamic process of the proliferative stage (mainly regulated by the Notch signaling pathway) and the stage of then differentiate into myotubes (mainly regulated by Wnt/β-catenin signaling pathway), and the "catalyst" of the key molecule β-catenin phosphorylation in Wnt/β-catenin signaling pathway, has a key role in the process.Objective:This study was designed to compare the endurance, the impact of resistance exercise on Wnt/β-catenin signaling pathway, and on Wnt/p-catenin pathway of skeletal muscle of PS1/PS2 double knockout mice. Aimed at provided theory and data support for exploring effective promote skeletal muscle remodeling and improve the movement of skeletal muscle homeostasis.Methods:Fifteen 6 months PS1/PS2 double knockout mice, as the experimental group, and fifteen the wild-type control mice were purchased from the Institute of Brain Functional Genes, and were randomly divided into three groups, a total of six groups: sedentary group (CC), endurance group CE (CE), resistance group CE (CR), double-tapping group (DC), double knock endurance group (DE), double knock resistance group (DR). Endurance group proceed to 10 weeks of treadmill running, speed at 0.8km / h, sustain 30min,3 times a week (Mondays, Wednesdays, Friday, beginning 18:00), trained 10 weeks in a total.The resistance group proceed to ladder climbing,4 per day, a group three times, each ladder top rest 1 min, rest between sets 2 min. Starting the negative weight of 50% of their body weight in mice, increasing 25 percent per week, increased to 100%. Control group do not exercise, other living conditions were equal with other groups.Results:1) Compared with Group CC, Wnt3a mRNA in Group DC was significantly reduced, Lrp6、Axin2、Gsk3β β-catenin mRNA expression increased relatively(β-catenin:P<0.05), Myf5, MyoD relative transcript levels were having up-regulated (no significant difference), Myogenin rised significantly (P<0.05); P-catenin total protein relative expression was upregulated, expression of p-β-catenin lowered and its phosphorylation level (p-β-catenin/β-catenin) was significantly lower (P<0.05), MyoD protein expression significantly increased (P<0.001).2) Compared with Group CC, Wnt3a, Lrp6, Gsk3β, β-catenin mRNA expression in group CE and CR increased relatively, group CR Wnt3a mRNA was significantly higher than the Group CC (P<0.05), CE group was significantly higher than group CR in Gsk3β mRNA (P<0.05),Axin2 relative expression was reduced (P>0.05), Pax7, Myf5, Myogenin, MyoD relative transcript levels were up-regulated (P>0.05); β-catenin phosphorylation levels tend to down, MyoD protein increased, but there was no significant difference. Compared with the Group DC, DE, group DR Lrp6, β-catenin mRNA reduced, Wnt3a, Axin2, Gsk3β mRNA upregulation, which Group DR Wnt3a transcript levels were significantly raised than Group DC (P<0.05), Pax7mRNA raised, group DE was significantly raised in Group DC (P<0.05), Myf5, MyoD trend lower (P>0.05), Myogenin significantly reduced(P< 0.01); p-β-catenin protein expression and p-ctaenin/β-catenin in group DE and DR was higher than Group DC(DE:P<0.05), MyoD protein expression reduced significantly lower among Group DR (P<0.01).3) IGF-1 mRNA:After exercise, group R is higher than in group C, group E (P<0.05), group E IGF-1 is slightly lower than in group C. Myostatin mRNA:E group was significantly lower than group C (P<0.05), compared with group C, R group relative expression decreased, but not significantly; IGF-1 protein:R group was significantly higher than group C (P<0.01), E group (P<0.05). Myostatin protein:Compared with group C, E, R group was lower (E:P<0.05, R:P>0.05).Conclusions:1) compared to resistance exercise, endurance exercise expression on the Wnt pathway target genes more apparent.2) PS1/PS2 knockout mice were significantly higher expression in skeletal muscle MyoD may appear excessive differentiation, while exercise may be through a mechanism (such as promoting degradation of P-catenin through intracellular ubiquitin-proteasome) to improve the Excessive differentiation state, and resistance exercise was better than endurance exercise significant.3) Two kinds of exercise are available to upregulate MyoD through the promotion of IGF-1, inhibit the upregulation of Myostatin, and MyoD increased expression may in some way make Myostatin upregulated.
Keywords/Search Tags:Endurance/resistance exercise, PS1/PS2 double knockout, Wnt signaling pathway, SC differentiation
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