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Dysregulation between TRIM63/FBXO32 expression and soleus muscle wasting in diabetic rats: potential role of miR-1-3p, -29a/b-3p, and -133a/b-3p

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Abstract

Diabetes mellitus (DM) induces a variable degree of muscle sarcopenia, which may be related to protein degradation and to the expression of both E3 ubiquitin ligases and some specific microRNAs (miRNAs). The present study investigated the effect of diabetes and acute muscle contraction upon the TRIM63 and FBXO32 expression as well as the potential involvement of some miRNAs. Diabetes was induced by streptozotocin and studied after 30 days. Soleus muscles were harvested, stimulated to contract in vitro for twitch tension analysis (0.5 Hz), 30 min later for tetanic analysis (100 Hz), and 30 min later were frozen. TRIM63 and FBXO32 proteins were quantified by western blotting; Trim63 mRNA, Fbxo32 mRNA, miR-1-3p, miR-29a-3p, miR-29b-3p, miR-133a-3p, and miR-133b-3p were quantified by qPCR. Diabetes induced sarcopenia by decreasing (P < 0.05) muscle weight/tibia length index, maximum tetanic contraction and relaxation rates, and absolute twitch and tetanic forces (P < 0.05). Diabetes decreased (P < 0.05) the Trim63 and Fbxo32 mRNAs (30%) and respective proteins (60%), and increased (P < 0.01) the miR-29b-3p (2.5-fold). In muscle from diabetic rats, acute contractile stimulus increased TRIM63 protein, miR-1-3p, miR-29a-3p, and miR-133a/b-3p, but decreased miR-29b-3p (P < 0.05). Independent of the metabolic condition, after muscle contraction, both TRIM63 and FBXO32 proteins correlated significantly with miR-1-3p, miR-29a/b-3p, and miR-133a/b-3p. All diabetes-induced regulations were reversed by insulin treatment. Concluding, the results depict that muscle wasting in long-term insulinopenic condition may not be accompanied by increased proteolysis, pointing out the protein synthesis as an important modulator of muscle sarcopenia in DM.

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Acknowledgements

This research was supported by the National Council for Scientific and Technological Development (CNPq) and by the São Paulo Research Foundation (FAPESP) #2012/04831-1. The authors are grateful to Dr. Antonio Carlos Oliveira and Ms. Carmen S. M. Serra for technical assistance and to Dr. Adauri Brezolin for English revision of the manuscript.

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  1. Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil

    Frederico Gerlinger-Romero, Caio Yogi Yonamine, Danilo Correa Pinto Junior, João Victor DelConti Esteves & Ubiratan Fabres Machado

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  1. Frederico Gerlinger-Romero
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Correspondence to Frederico Gerlinger-Romero.

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Gerlinger-Romero, F., Yonamine, C.Y., Junior, D.C.P. et al. Dysregulation between TRIM63/FBXO32 expression and soleus muscle wasting in diabetic rats: potential role of miR-1-3p, -29a/b-3p, and -133a/b-3p. Mol Cell Biochem 427, 187–199 (2017). https://doi.org/10.1007/s11010-016-2910-z

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