Amyotrophic lateral sclerosis associated disturbance of iron metabolism is blunted by swim training-role of AKT signaling pathway.

Autor: Halon-Golabek M; Department of Physiotherapy, Faculty of Health Sciences, Medical University of Gdansk, Gdansk, Poland., Flis DJ; Department of Pharmaceutical Pathophysiology, Faculty of Pharmacy, Medical University of Gdansk, Gdansk, Poland., Zischka H; Institute of Molecular Toxicology and Pharmacology, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Toxicology and Environmental Hygiene, Technical University Munich, School of Medicine, Munich, Germany., Akdogan B; Institute of Molecular Toxicology and Pharmacology, Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany., Wieckowski MR; Laboratory of Mitochondrial Biology and Metabolism, Nencki Institute of Experimental Biology, Warsaw, Poland., Antosiewicz J; Department of Bioenergetics and Physiology of Exercise, Faculty of Health Sciences, Medical University of Gdansk, Gdansk, Poland. Electronic address: jedrzej.antosiewicz@gumed.edu.pl., Ziolkowski W; Department of Rehabilitation Medicine, Faculty of Health Sciences Medical University of Gdansk, Gdansk, Poland. Electronic address: wieslaw.ziolkowski@gumed.edu.pl.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2024 Mar; Vol. 1870 (3), pp. 167014. Date of Electronic Publication: 2024 Jan 01.
DOI: 10.1016/j.bbadis.2023.167014
Abstrakt: Swim training has increased the life span of the transgenic animal model of amyotrophic lateral sclerosis (ALS). Conversely, the progress of the disease is associated with the impairment of iron metabolism and insulin signaling. We used transgenic hmSOD1 G93A (ALS model) and non-transgenic mice in the present study. The study was performed on the muscles taken from trained (ONSET and TERMINAL) and untrained animals at three stages of the disease: BEFORE, ONSET, and TERMINAL. In order to study the molecular mechanism of changes in iron metabolism, we used SH-SY5Y and C2C12 cell lines expression vector pcDNA3.1 and transiently transfected with specific siRNAs. The progress of ALS resulted in decreased P-Akt/Akt ratio, which is associated with increased proteins responsible for iron storage ferritin L, ferritin H, PCBP1, and skeletal muscle iron at ONSET. Conversely, proteins responsible for iron export- TAU significantly decrease. The training partially reverses changes in proteins responsible for iron metabolism. AKT silencing in the SH-SY5Y cell line decreased PCBP2 and ferroportin and increased ferritin L, H, PCBP1, TAU, transferrin receptor 1, and APP. Moreover, silencing APP led to an increase in ferritin L and H. Our data suggest that swim training in the mice ALS model is associated with significant changes in iron metabolism related to AKT activity. Down-regulation of AKT mainly upregulates proteins involved in iron import and storage but decreases proteins involved in iron export.
Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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