Denervation-induced muscle atrophy suppression in renalase-deficient mice via increased protein synthesis.

Abstract

Denervation-induced muscle atrophy increases signaling through both protein degradation and synthesis pathways. Renalase is a flavin adenine dinucleotide-dependent amine oxidase that inhibits apoptosis and inflammation and promotes cell survival. This study aimed to elucidate the effect of renalase on denervation-induced muscle atrophy. We used 7-week-old renalase knock-out (KO) mice (a model of denervation-induced muscle atrophy) and wild-type (WT) mice (KO: n = 6, weight = 20-26 g; WT: n = 5, weight = 19-23 g). After their left legs were denervated, these mice were killed 1 week later. KO mice had lighter muscle weight than the WT mice. We observed an increase in molecular signaling through protein degradation pathway as well as oxidative stress in denervated muscles compared with that in sham-operated muscles in both WT and KO mice. Additionally, we also observed the main effect of renalase in WT and KO mice. Mitochondrial oxidative phosphorylation protein content was lower in denervated muscles than in sham-operated muscles in both WT and KO mice. However, a significant difference was noted in the reaction with Akt and p70S6K (components of the protein synthesis pathway) between WT and KO mice. In conclusion, mice with renalase deficiency demonstrated an attenuation of denervation-induced muscle atrophy. This might be related to catecholamines because signaling through the protein synthesis pathway was increased following denervation in renalase KO mice compared with that in WT mice, despite showing no change in signaling through protein degradation pathways.

• Authors: Katsuyuki Tokinoya, Takanaga Shirai, Yuya Ota, Tohru Takemasa, Kazuhiro Takekoshi
• Journal: Physiological reports (Physiol Rep) Vol. 8 Issue 15 Pg. e14475 (08 2020) ISSN: 2051-817X [Electronic] United States
• PMID: 32741114 (Publication Type: Journal Article)
• Copyright: © 2020 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.

Chemical References

• Monoamine Oxidase
• renalase
• Proto-Oncogene Proteins c-akt
• Ribosomal Protein S6 Kinases, 70-kDa

Topics

• Animals
• Denervation (adverse effects)
• Male
• Mice
• Mitochondria, Muscle (metabolism)
• Monoamine Oxidase (deficiency, genetics, metabolism)
• Muscle, Skeletal (metabolism)
• Muscular Atrophy (etiology, genetics, metabolism)
• Oxidative Phosphorylation
• Protein Biosynthesis
• Proto-Oncogene Proteins c-akt (metabolism)
• Ribosomal Protein S6 Kinases, 70-kDa (metabolism)
• Signal Transduction