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Attractin deficiency causes metabolic and morphological abnormalities in slow-twitch muscle

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Abstract

Skeletal muscle fibers are classified as slow-twitch and fast-twitch fibers, which have different reactive oxygen species (ROS) metabolism and mitochondrial biogenesis. Recently, Attractin (Atrn), which encodes secreted (sAtrn) and transmembrane (mAtrn)-type proteins, has been shown to be involved in free radical scavenging. Although Atrn has been found in skeletal muscle, little is known about the expression levels and function of Atrn in each muscle fiber type. Therefore, we investigate sAtrn and mAtrn expression levels in the slow-twitch soleus (sol) and fast-twitch extensor digitorum longus (EDL) muscles as well as the morphology and expression levels of antioxidant enzymes and functional mitochondrial markers using Atrn-deficient muscles. Both types of Atrn were expressed in the sol and EDL. mAtrn was mainly expressed in the adult sol, whereas sAtrn expression levels did not differ between muscle types. Moreover, mAtrn in the sol was abundantly localized in the subsarcolemmal area, especially in the myoplasm near mitochondria. Atrn-deficient Zitter rats showed muscle fiber atrophy, myofibril misalignment, mitochondrial swelling and vacuolation in the sol but not EDL. Furthermore, the Atrn-deficient sol exhibited a marked reduction in antioxidant enzyme SOD1, GPx1, catalase and Prx6 and mitochondrial functional protein, UCP2, expression. Even Atrn-deficient EDL showed a significant reduction in Prx3, Prx6, UCP2 and UCP3 expression. These data indicate that Atrn-deficiency disturbs ROS metabolism in skeletal muscles. In particular, mAtrn is involved in metabolism in the slow-twitch sol muscle and mAtrn-deficiency may cause ROS imbalance, resulting in morphological abnormalities in the muscle.

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Acknowledgements

The authors would like to express their gratitude to Mr. Masahiro Takano (Teikyo University Mechanical Factory) for manufacturing the cryomill, Ms. Shukuko Minami for her technical assistance and Ms. Fusae Terauchi for her assistance with manuscript preparation.

Funding

This work was supported by a research grant from Dokkyo Medical University.

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Authors and Affiliations

  1. Department of Histology and Neurobiology, Dokkyo Medical University School of Medicine, 880 Kita-Kobayashi, Mibu, 321-0293, Tochigi, Japan

    Ayuka Ehara, Daisuke Taguchi & Shuichi Ueda

  2. Department of Judo Therapy, Faculty of Medical Technology, Teikyo University, 1-1 Toyosatodai, Utsunomiya-shi, 320-8551, Tochigi, Japan

    Daisuke Taguchi

  3. Department of Basic Science, Educational and Research Center for Pharmacy , Meiji Pharmaceutical University , 2-522-1 Noshio, Kiyose-shi, 204- 8588, Tokyo, Japan

    Kazuhiko Nakadate

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  1. Ayuka Ehara
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  2. Daisuke Taguchi
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Correspondence to Ayuka Ehara.

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All procedures performed involving animals were in accordance with NIH guidelines and approved by the Animal Welfare Committee at Dokkyo University School of Medicine (approval no. 0570).

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Ehara, A., Taguchi, D., Nakadate, K. et al. Attractin deficiency causes metabolic and morphological abnormalities in slow-twitch muscle. Cell Tissue Res 384, 745–756 (2021). https://doi.org/10.1007/s00441-021-03423-w

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