Sodium fluoride induces skeletal muscle atrophy via changes in mitochondrial and sarcomeric proteomes

Apoorva H Nagendra; Animikh Ray; Debajit Chaudhury; Akash Mitra; Anu Vinod Ranade; Bipasha Bose; Sudheer Shenoy P

doi:10.1371/journal.pone.0279261

Sodium fluoride induces skeletal muscle atrophy via changes in mitochondrial and sarcomeric proteomes

PLoS One. 2022 Dec 22;17(12):e0279261. doi: 10.1371/journal.pone.0279261. eCollection 2022.

Authors

Apoorva H Nagendra¹, Animikh Ray², Debajit Chaudhury¹, Akash Mitra¹, Anu Vinod Ranade³, Bipasha Bose¹, Sudheer Shenoy P¹

Affiliations

¹ Stem Cells and Regenerative Medicine Centre, Yenepoya Research Centre, Yenepoya Deemed to be University, Deralakatte, Mangalore, India.
² Father Muller Research Centre, Father Muller Medical College, Father Muller Charitable Institutions, Kankanady, Mangalore, Karnataka, India.
³ Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.

Abstract

Sodium Fluoride (NaF) can change the expression of skeletal muscle proteins. Since skeletal muscle is rich in mitochondrial and contractile (sarcomeric) proteins, these proteins are sensitive to the effects of NaF, and the changes are dose-and time-dependent. In the current study, we have analysed the effect of high concentrations of NaF (80ppm) on mouse skeletal muscle at two different time points, i.e., 15 days and 60 days. At the end of the experimental time, the animals were sacrificed, skeletal muscles were isolated, and proteins were extracted and subjected to bioinformatic (Mass Spectrometric) analysis. The results were analysed based on changes in different mitochondrial complexes, contractile (sarcomeric) proteins, 26S proteasome, and ubiquitin-proteasome pathway. The results showed that the mitochondrial proteins of complex I, II, III, IV and V were differentially regulated in the groups treated with 80ppm of NaF for 15 days and 60 days. The network analysis indicated more changes in mitochondrial proteins in the group treated with the higher dose for 15 days rather than 60 days. Furthermore, differential expression of (sarcomeric) proteins, downregulation of 26S proteasome subunits, and differential expression in proteins related to the ubiquitin-proteasome pathway lead to muscle atrophy. The differential expression might be due to the adaptative mechanism to counteract the deleterious effects of NaF on energy metabolism. Data are available via ProteomeXchange with identifier PXD035014.

Copyright: © 2022 Nagendra et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Mice
Mitochondrial Proteins / metabolism
Muscle, Skeletal* / drug effects
Muscle, Skeletal* / metabolism
Muscular Atrophy* / chemically induced
Proteasome Endopeptidase Complex* / metabolism
Proteome / metabolism
Sodium Fluoride* / pharmacology
Ubiquitin / metabolism

Substances

Mitochondrial Proteins
Proteasome Endopeptidase Complex
Proteome
Sodium Fluoride
Ubiquitin

Grants and funding

This research was funded by the Department of Science and Technology (DST, EMR/2017/000591) Government of India, and Yenepoya Deemed to be University seed grant funding (YU/SG/111/2022) awarded to the principal investigator (Dr. Sudheer Shenoy P, CO-PI: Dr. Bipasha Bose). Apoorva HN, Junior research fellow, was supported by the DST grant fellowship. The study was also partly funded by the collaborative grant No. 1901090160 from University of Sharjah UAE awarded to the principal investigator (Dr. Anu Vinod Ranade).