Identification and functional characterization of TRPA1 in human myoblasts

Abstract

The proper function of the skeletal muscle is essential for the survival of most animals. Thus, efficient and rapid repair of muscular damage following injury is crucial. In recent years, satellite cells have emerged as key players of muscle repair, capable of undergoing extensive proliferation after injury, fusing into myotubes and restoring muscle function. Furthermore, it has been shown that Ca(2+)/calmodulin-dependent generation of nitric oxide (NO) is an important regulator of muscle repair. Here, we demonstrate the functional expression of transient receptor potential, subfamily A1 (TRPA1) channel in human primary myoblasts. Stimulation of these cells with well-known TRPA1 ligands led to robust intracellular Ca(2+) rises which could be inhibited by specific TRPA1 antagonists. Moreover, we show that TRPA1 activation enhances important aspects of skeletal muscle repair such as cell migration and myoblast fusion in vitro. Interestingly, TRPA1 levels and inducible Ca(2+) transients decline with ongoing myoblast differentiation. We suggest that TRPA1 might serve as a physiological mediator for inflammatory signals and appears to have a functional role in promoting myoblast migration, fusion, and potentially also in activating satellite cells in humans.

The Hypothermic Effect of Hydrogen Sulfide Is Mediated by the Transient Receptor Potential Ankyrin-1 Channel in Mice

“…In accordance with the higher sensitivity, with RNAscope we detected some Trpa1 mRNA transcripts in all of the studied brain nuclei within the autonomic thermoregulatory pathways. The low-abundance expression of Trpa1 mRNA in the studied thermoregulatory brain structures may indicate that these neurons play a minor role in the effect of H 2 S, but it has to be noted that mRNA expression does not necessarily correlate with the rate of protein translation, since a low mRNA expression can be associated with high protein levels, as shown in different studies [ 57 , 61 ]. Importantly, despite its low mRNA expression, TRPA1 is thought to play critical physiological functions in various tissues [ 57 , 61 , 62 , 63 ].…”

Contractile function recovery in severely injured gastrocnemius muscle of rats treated with either oleic or linoleic acid

“…Along with these events, re-innervation, angiogenesis and extracellular matrix remodelling take place in order to promote full recovery of the injured muscle tissue and muscle function (Fukushima et al 2001;Charge & Rudnicki, 2004;Ciciliot & Schiaffino, 2010;Mann et al 2011). Although the underlying mechanisms involved in the regeneration are not completely understood, several key proteins have been described to participate in this process, including striated muscle activator of Rho signalling, serumand glucocorticoid-inducible kinase-1, phosphatase and tensin homologue, the Notch pathway, latent transforming growth factor-β binding protein-4/transforming growth factor-β signalling, and transient receptor potential channel subfamily A1 (Hu et al 2010;Church et al 2014;Lamon et al 2014;Swaggart & McNally, 2014;Steinberger et al 2015;Osterloh et al 2016;Wallace et al 2016). Severe injuries (e.g.…”

ERK Phosphorylation Regulates the Aml1/Runx1 Splice Variants and the TRP Channels Expression during the Differentiation of Glioma Stem Cell Lines

“…In pain-sensitive nerve endings, TRPA1 senses the oxidative stress and transduces it into neural signals [47]; similarly, in GBM, oxidative stress activates TRPA1 channels [48]. Chemical stimulation of TRPA1 seems to activate stem cells [49] and at least in skeletal muscle, TRPA1 agonists stimulate migration and early stem cell differentiation [50]. Moreover, recently, a crosstalk between Runx1 and TGFβ signaling pathway regulating the TRPA1 and TRPV1 expression and an increased Ca 2+ activity was evidenced during megakaryocyte differentiation and silencing of Aml1/Runx1 markedly reduced the TRPA1 and TRPV1 mRNA expression [51].…”