Ohno Yoshitaka, Sugiura Takao, Ohira Yoshinobu, Yoshioka Toshitada, Goto Katsumasa
Laboratory of Physiology, School of Health Sciences, Toyohashi SOZO University, Toyohashi, 440-8511, Japan.
Faculty of Education, Yamaguchi University, Yamaguchi, 753-8513, Japan.
Physiol Rep. 2014 Dec 24;2(12). doi: 10.14814/phy2.12259. Print 2014 Dec 1.
Effects of mechanical loading on the expression level of tripartite motif-containing 72 (TRIM72) and caveolin-3 (Cav-3) in mouse soleus muscle were investigated. Mice were subjected to (1) continuous hindlimb suspension (HS) for 2 weeks followed by 1-week ambulation recovery or (2) functional overloading (FO) on the soleus by cutting the distal tendons of the plantaris and gastrocnemius muscles. Soleus muscle atrophy was induced by 2-week hindlimb suspension (HS). Reloading-associated regrowth of atrophied soleus muscle was observed by 1-week reloading following HS. HS also depressed the expression level of insulin receptor substrate-1 (IRS-1) mRNA, TRIM72, Cav-3, and phosphorylated Akt (p-Akt)/total Akt (t-Akt), but increased the phosphorylated level of p38 mitogen-activated protein kinase (p-p38MAPK) in soleus muscle. Thereafter, the expression level of MyoD mRNA, TRIM72 (mRNA, and protein), and Cav-3 was significantly increased and recovered to the basal level during 1-week reloading after HS. Although IRS-1 expression was also upregulated by reloading, the expression level was significantly lower than that before HS. Significant increase in p-Akt and phosphorylated p70 S6 kinase (p-p70S6K) was observed by 1-day reloading. On the other hand, 1-week functional overloading (FO) induced soleus muscle hypertrophy. In FO-associated hypertrophied soleus muscle, the expression level of IRS-1 mRNA, MyoD mRNA, TRIM72 mRNA, p-Akt, and p-p70S6K was increased, but the expression of Cav-3 and p-p38MAPK was decreased. FO had no effect on the protein expression level of TRIM72. These observations suggest that the loading-associated upregulation of TRIM72 protein in skeletal muscle may depress the regrowth of atrophied muscle via a partial suppression of IRS-1. In addition, downregulation of Cav-3 in skeletal muscle may depress overloading-induced muscle hypertrophy.
研究了机械负荷对小鼠比目鱼肌中含三联基序蛋白72（TRIM72）和小窝蛋白3（Cav - 3）表达水平的影响。将小鼠分为两组：（1）连续后肢悬吊（HS）2周，随后进行1周的行走恢复；（2）通过切断跖肌和腓肠肌的远端肌腱对比目鱼肌进行功能性超负荷（FO）处理。2周的后肢悬吊（HS）诱导了比目鱼肌萎缩。HS后1周的再负荷观察到萎缩比目鱼肌的再生长。HS还降低了比目鱼肌中胰岛素受体底物-1（IRS - 1）mRNA、TRIM72、Cav - 3以及磷酸化Akt（p - Akt）/总Akt（t - Akt）的表达水平，但增加了p38丝裂原活化蛋白激酶（p - p38MAPK）的磷酸化水平。此后，HS后1周的再负荷期间，MyoD mRNA、TRIM72（mRNA和蛋白质）和Cav - 3的表达水平显著增加并恢复到基础水平。尽管再负荷也上调了IRS - 1的表达，但表达水平显著低于HS前。再负荷1天观察到p - Akt和磷酸化p70核糖体蛋白S6激酶（p - p70S6K）显著增加。另一方面，1周的功能性超负荷（FO）诱导了比目鱼肌肥大。在FO相关的肥大比目鱼肌中，IRS - 1 mRNA、MyoD mRNA、TRIM72 mRNA、p - Akt和p - p70S6K的表达水平增加，但Cav - 3和p - p38MAPK的表达降低。FO对TRIM72的蛋白表达水平无影响。这些观察结果表明，骨骼肌中TRIM72蛋白的负荷相关上调可能通过部分抑制IRS - 1来抑制萎缩肌肉的再生长。此外，骨骼肌中Cav - 3的下调可能抑制超负荷诱导的肌肉肥大。
