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. 2018 Sep 27;19(10):2954.
doi: 10.3390/ijms19102954.

AMPK Mediates Muscle Mass Change But Not the Transition of Myosin Heavy Chain Isoforms during Unloading and Reloading of Skeletal Muscles in Mice

Tatsuro Egawa  1   2   3 , Yoshitaka Ohno  4 , Ayumi Goto  5   6 , Shingo Yokoyama  7 , Tatsuya Hayashi  8 , Katsumasa Goto  9   10
Affiliations

AMPK Mediates Muscle Mass Change But Not the Transition of Myosin Heavy Chain Isoforms during Unloading and Reloading of Skeletal Muscles in Mice

Tatsuro Egawa et al. Int J Mol Sci. .

Abstract

5'AMP-activated protein kinase (AMPK) plays an important role in the regulation of skeletal muscle mass and fiber-type distribution. However, it is unclear whether AMPK is involved in muscle mass change or transition of myosin heavy chain (MyHC) isoforms in response to unloading or increased loading. Here, we checked whether AMPK controls muscle mass change and transition of MyHC isoforms during unloading and reloading using mice expressing a skeletal-muscle-specific dominant-negative AMPKα1 (AMPK-DN). Fourteen days of hindlimb unloading reduced the soleus muscle weight in wild-type and AMPK-DN mice, but reduction in the muscle mass was partly attenuated in AMPK-DN mice. There was no difference in the regrown muscle weight between the mice after 7 days of reloading, and there was concomitantly reduced AMPKα2 activity, however it was higher in AMPK-DN mice after 14 days reloading. No difference was observed between the mice in relation to the levels of slow-type MyHC I, fast-type MyHC IIa/x, and MyHC IIb isoforms following unloading and reloading. The levels of 72-kDa heat-shock protein, which preserves muscle mass, increased in AMPK-DN-mice. Our results indicate that AMPK mediates the progress of atrophy during unloading and regrowth of atrophied muscles following reloading, but it does not influence the transition of MyHC isoforms.

Keywords: atrophy; fiber-type; heat shock protein; peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α); regrowth; sirtuin 1 (SIRT1).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Summary of the experimental protocol. The hindlimbs of both dominant-negative mutant of AMPK (AMPK-DN) and wild-type littermate (WT) mice were continuously suspended for 14 days. After 14 days, the mice were allowed ambulation recovery. Pre: before hindlimb suspension; R0, R7, and R14: 0, 7, and 14 days after ambulation recovery; n = 8 per group.
Figure 2
Figure 2
Changes in the isoform-specific 5′AMP-activated protein kinase (AMPK) activity after 14 days of hindlimb unloading, and at 0, 7, and 14 days of reloading. (A) AMPKα1 activity. (B) AMPKα2 activity. Values are means ± SE; n = 7–8 per group. Statistical results of two-way ANOVA (genotype, time, and genotype × time) are described in the Figure. *, significant difference between genotypes at same time point. ¶, significant difference from R0 independent of genotype, unless special mention in Figure.
Figure 3
Figure 3
Changes in the body weight and soleus weight after 14 days of hindlimb unloading, and at 0, 7, and 14 days of reloading. (A) Body weight. (B) Relative soleus weight to body weight. Values are means ± SE; n = 8 per group. Statistical results of two-way ANOVA (genotype, time, and genotype × time) are described in the Figure. *, significant difference between genotypes at same time point. †, significant difference from Pre independent of genotype. ¶, significant difference from R0 independent of genotype.
Figure 4
Figure 4
Changes in relative levels of myosin heavy chain (MyHC) isoforms in the soleus muscles after 14 days of hindlimb unloading, and at 0, 7, and 14 days of reloading. (A) MyHC I. (B) MyHC IIa/x. (C) MyHC IIb. Representative image is shown. Values are means ± SE; n = 8 per group. Statistical results of two-way ANOVA (genotype, time, and genotype × time) are described in the Figure. †, significant difference from Pre independent of genotype.
Figure 5
Figure 5
Changes in sirtuin 1 (SIRT1) activity and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) mRNA expression after 14 days of hindlimb unloading, and at 0, 7, and 14 days of reloading. (A) SIRT1 activity; n = 3 per group. (B) PGC1α mRNA; n = 8 per group. Values are means ± SE. Statistical results of two-way ANOVA (genotype, time, and genotype × time) are described in the Figure. †, significant difference from Pre independent of genotype. ¶, significant difference from R0 independent of genotype.
Figure 6
Figure 6
Changes in the 72-kDa heat shock protein (HSP72) expression after 14 days of hindlimb unloading, and at 0, 7, and 14 days of reloading. Representative immunoblots are shown. Values are means ± SE. Statistical results of two-way ANOVA (genotype, time, and genotype × time) are described in the Figure. †, significant difference from Pre independent of genotype. ¶, significant difference from R0 independent of genotype.
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