Cited by 80Muscle Physiology and DisordersInflammatory mediators and NSAID effectsFatty Acid Research and Health

Arachidonic Acid Supplementation Enhances in Vitro Skeletal Muscle Cell Growth Via a COX-2-Dependent Pathway

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Markworth, James F., Cameron-Smith, David·2013·American Journal of Physiology-Cell Physiology

Abstract

Arachidonic acid (AA) is the metabolic precursor to a diverse range of downstream bioactive lipid mediators. A positive or negative influence of individual eicosanoid species [e.g., prostaglandins (PGs), leukotrienes, and hydroxyeicosatetraenoic acids] has been implicated in skeletal muscle cell growth and development. The collective role of AA-derived metabolites in physiological states of skeletal muscle growth/atrophy remains unclear. The present study aimed to determine the direct effect of free AA supplementation and subsequent eicosanoid biosynthesis on skeletal myocyte growth in vitro. C2C12 (mouse) skeletal myocytes induced to differentiate with supplemental AA exhibited dose-dependent increases in the size, myonuclear content, and protein accretion of developing myotubes, independent of changes in cell density or the rate/extent of myogenic differentiation. Nonselective (indomethacin) or cyclooxygenase 2 (COX-2)-selective (NS-398) nonsteroidal anti-inflammatory drugs blunted basal myogenesis, an effect that was amplified in the presence of supplemental free AA substrate. The stimulatory effects of AA persisted in preexisting myotubes via a COX-2-dependent (NS-389-sensitive) pathway, specifically implying dependency on downstream PG biosynthesis. AA-stimulated growth was associated with markedly increased secretion of PGF(2α) and PGE(2); however, incubation of myocytes with PG-rich conditioned medium failed to mimic the effects of direct AA supplementation. In vitro AA supplementation stimulates PG release and skeletal muscle cell hypertrophy via a COX-2-dependent pathway.

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Registry

Crossref · 10.1152/ajpcell.00038.2012

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  • Arachidonic acid supplementation enhances C2C12 myotubes cell growth and development via cyclooxygenase-2-dependent pathway.

    “Arachidonic acid (5,8,11,14-eicosatetraenoic acid C20:4, omega-6) supplementation enhances C2C12 myotubes cell growth and development via cyclooxygenase-2-dependent pathway [80].”

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Authors
Markworth, J. F., & Cameron-Smith, D.
Affiliations
  • Deakin University (AU)
  • Liggins Institute, University of Auckland, Auckland, New Zealand
Venue
American Journal of Physiology-Cell Physiology
Published
2013-01-01
Volume
304
Issue
1
Pages
C56-C67
ISSN
  • 0363-6143 (ISSN-L)
  • 1522-1563
OpenAlex
W2049005289
Cited by
80
References
61
Citations by year
2026: 8 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 5 · 2021: 7 · 2020: 4 · 2019: 1 · 2018: 12 · 2017: 5 · 2016: 7 · 2015: 5 · 2014: 6 · 2013: 4
FWCI
1.93
Type
journal article
Language
en
Open access
Locations
  • American Journal of Physiology-Cell Physiology (publishedVersion)
  • PubMed (publishedVersion)
  • Deakin Research Online (Deakin University)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Keywords
arachidonic acid, myotube hypertrophy, cyclooxygenase-2, prostaglandins, eicosanoids, myogenesis, C2C12 myocytes, nonsteroidal anti-inflammatory drugs, indomethacin, NS-398, PGF2alpha, prostaglandin E2, muscle atrophy
MeSH terms
Animals, Cell Differentiation, Cell Survival, Cells, Cultured, Hypertrophy, Dinoprostone, Dinoprost, Signal Transduction, Arachidonic Acid, Muscle Fibers, Skeletal, Cell Enlargement, Mice, Cyclooxygenase 2

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