Arachidonic Acid Supplementation Enhances in Vitro Skeletal Muscle Cell Growth Via a COX-2-Dependent Pathway
Open accessAbstract
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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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].”
From Nutraceuticals in the Prevention and Treatment of the Muscle Atrophy (2021) · cites this paper as [80]
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Arachidonic Acid Structure and Synthesis
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- Authors
- Markworth, J. F., & Cameron-Smith, D.
- Affiliations
- Deakin University (AU)
- Liggins Institute, University of Auckland, Auckland, New Zealand
- ORCID
- Markworth, James F.
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- 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
- green
- doi.org
- 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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