Publication:
The Impact of Melatonin and NLRP3 Inflammasome on the Expression of microRNAs in Aged Muscle

Loading...
Thumbnail Image

Date

2021-03-27

Authors

Sayed, Ramy KA
Fernández-Ortiz, Marisol
Fernández-Martínez, José
Aranda Martínez, Paula
Guerra-Librero, Ana
Rodríguez-Santana, César
de Haro, Tomás
Escames, Germaine
Acuña-Castroviejo, Darío
Rusanova, Iryna

Advisors

Journal Title

Journal ISSN

Volume Title

Publisher

MDPI
Metrics
Google Scholar
Export

Research Projects

Organizational Units

Journal Issue

Abstract

Muscular aging is a complex process and underlying physiological mechanisms are not fully clear. In recent years, the participation of the NF-kB pathway and the NLRP3 inflammasome in the chronic inflammation process that accompanies the skeletal muscle's aging has been confirmed. microRNAs (miRs) form part of a gene regulatory machinery, and they control numerous biological processes including inflammatory pathways. In this work, we studied the expression of four miRs; three of them are considered as inflammatory-related miRs (miR-21, miR-146a, and miR-223), and miR-483, which is related to the regulation of melatonin synthesis, among other targets. To investigate the changes of miRs expression in muscle along aging, the impact of inflammation, and the role of melatonin in aged skeletal muscle, we used the gastrocnemius muscle of wild type (WT) and NLRP3-knockout (NLRP3-) mice of 3, 12, and 24 months-old, with and without melatonin supplementation. The expression of miRs and pro-caspase-1, caspase-3, pro-IL-1β, bax, bcl-2, and p53, was investigated by qRT-PCR analysis. Histological examination of the gastrocnemius muscle was also done. The results showed that age increased the expression of miR-21 (p < 0.01), miR-146a, and miR-223 (p < 0.05, for both miRs) in WT mice, whereas the 24-months-old mutant mice revealed decline of miR-21 and miR-223 (p < 0.05), compared to WT age. The lack of NLRP3 inflammasome also improved the skeletal muscle fibers arrangement and reduced the collagen deposits compared with WT muscle during aging. For the first time, we showed that melatonin significantly reduced the expression of miR-21, miR-146a, and miR-223 (p < 0.05 for all ones, and p < 0.01 for miR-21 at 24 months old) in aged WT mice, increased miR-223 in NLRP3- mice (p < 0.05), and induced miR-483 expression in both mice strains, this increase being significant at 24 months of age.

Description

MeSH Terms

Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Multiprotein Complexes::Inflammasomes
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Apoptosis Regulatory Proteins::Caspases::Caspases, Initiator::Caspase 1
Medical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Melatonin
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::NF-kappa B
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Apoptosis Regulatory Proteins::Caspases::Caspases, Effector::Caspase 3
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Neoplasm Proteins::Tumor Suppressor Proteins::Tumor Suppressor Protein p53
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intracellular Signaling Peptides and Proteins::Apoptosis Regulatory Proteins::Proto-Oncogene Proteins c-bcl-2::bcl-2-Associated X Protein
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, Antisense::MicroRNAs
Medical Subject Headings::Anatomy::Musculoskeletal System::Muscles::Muscle, Skeletal
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Inflammation
Medical Subject javascript:void(null);Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Scleroproteins::Extracellular Matrix Proteins::Collagen
Medical Subject Headings::Anatomy::Tissues::Muscles::Muscle, Striated::Muscle, Skeletal::Muscle Fibers, Skeletal
Medical Subject Headings::Phenomena and Processes::Biological Phenomena
Medical Subject Headings::Technology and Food and Beverages::Food and Beverages::Food::Dietary Supplements
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Cytokines::Interleukins::Interleukin-1
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction

DeCS Terms

CIE Terms

Keywords

microRNAs, Melatonin, NLRP3 inflammasome, NF-kB, Aging, Pro-caspase-1, Caspase-3, bcl-2, Muscle fibers, Collagen, MicroARNs, Melatonina, Proteína con dominio pirina 3 de la familia NLR, FN-kappa B, Envejecimiento, Caspasa 1, Caspasa 3, Fibras Musculares Esqueléticas

Citation

Sayed RK, Fernández-Ortiz M, Fernández-Martínez J, Aranda Martínez P, Guerra-Librero A, Rodríguez-Santana C, et al. The Impact of Melatonin and NLRP3 Inflammasome on the Expression of microRNAs in Aged Muscle. Antioxidants (Basel). 2021 Mar 27;10(4):524