Profiling of adenine‐derived signaling molecules, cytokinins, in myotubes reveals fluctuations in response to lipopolysaccharide‐induced cell stress

Cytokinins (CTKs) are a diverse collection of evolutionarily conserved adenine‐derived signaling molecules classically studied as phytohormones; however, their roles and production have been less studied in mammalian systems. Skeletal muscles are sensitive to cellular cues such as inflammation and i...

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Published in:Physiological reports 2023-12, Vol.11 (23), p.e15870-n/a
Main Authors: Tobin, Stephanie W., Seneviratne, Dev, Phan, Lorna, Seegobin, Mark, Rico, Alexander L., Westby, Beth, Kisiala, Anna, Martic, Sanela, Brunetti, Craig R., Emery, R. J. Neil
Format: Article
Language:English
Subjects:
Adenine - pharmacology
Cellular stress response
cytokinin
Cytokinins
Cytokinins - chemistry
Extracellular levels
High-performance liquid chromatography
Kinases
Life sciences
Lipopolysaccharides
Lipopolysaccharides - pharmacology
Mammalian cells
Mass spectroscopy
Metabolomics
muscle
Muscle Fibers, Skeletal
Myogenesis
myokine
Myotubes
Original
Secretome
Skeletal muscle
Transfer RNA
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Summary:Cytokinins (CTKs) are a diverse collection of evolutionarily conserved adenine‐derived signaling molecules classically studied as phytohormones; however, their roles and production have been less studied in mammalian systems. Skeletal muscles are sensitive to cellular cues such as inflammation and in response, alter their secretome to regulate the muscle stem cell and myofiber niche. Using cultured C2C12 muscle cells, we profiled CTK levels to understand (1) whether CTKs are part of the muscle secretome and (2) whether CTKs are responsive to cellular stress. To induce cellular stress, C2C12 myotubes were treated with lipopolysaccharides (LPS) for 24 h and then media and cell fractions were collected for ultra high‐performance liquid chromatography tandem mass spectrometry with electrospray ionization (UHPLC‐(ESI+)‐HRMS/MS) for metabolomics and CTK profiling. Across LPS‐treated and control cells, 11 CTKs were detected in the extracellular space while 6 were detected intracellularly. We found that muscle cells are enriched in isopentenyladenine (iP) species (from free base, riboside to nucleotide forms), and that extracellular levels are increased after LPS treatment. Our study establishes that muscle cells express various forms of CTKs, and that CTK levels are responsive to LPS‐induced cell stress, suggesting a role for CTKs in intra‐ and extracellular signaling of mammalian cells.
ISSN:2051-817X
DOI:10.14814/phy2.15870