Continuous mild heat stress induces differentiation of mammalian myoblasts, shifting fiber type from fast to slow

Abstract

Yamaguchi T, Suzuki T, Arai H, Tanabe S, Atomi Y. Continuous mild heat stress induces differentiation of mammalian myoblasts, shifting fiber type from fast to slow. Am J Physiol Cell Physiol 298: C140 -C148, 2010. First published July 15, 2009; doi:10.1152/ajpcell.00050.2009.-Local hyperthermia has been widely used as physical therapy for a number of diseases such as inflammatory osteoarticular disorders, tendinitis, and muscle injury. Local hyperthermia is clinically applied to improve blood and lymphatic flow to decrease swelling of tissues (e.g., skeletal muscle). As for muscle repair following injury, the mechanisms underlying the beneficial effects of hyperthermia-induced muscle repair are unknown. In this study, we investigated the direct effects of continuous heat stress on the differentiation of cultured mammalian myoblasts. Compared with control cultures grown at 37°C, incubation at 39°C (continuous mild heat stress; CMHS) enhanced myotube diameter, whereas myotubes were poorly formed at 41°C by primary human skeletal muscle culture cells, human skeletal muscle myoblasts (HSMMs), and C2C12 mouse myoblasts. In HSMMs and C2C12 cells exposed to CMHS, mRNA and protein levels of myosin heavy chain (MyHC) type I were increased compared with the control cultures. The mRNA level of MyHC IIx was unaltered in HSMMs and decreased in C2C12 cells, compared with cells that were not exposed to heat stress. These results indicated a fast-to-slow fiber-type shift in myoblasts. We also examined upstream signals that might be responsible for the fast-to-slow shift of fiber types. CMHS enhanced the mRNA and protein levels of peroxisome proliferator-activated receptor-␥ coactivator (PGC)-1␣ in HSMMS and C2C12 cells but not the activities of MAPKs (ERK1/2 and p38 MAPK) in HSMMs and C2C12 cells. These data suggest that CMHS induces a fast-to-slow fiber-type shift of mammalian myoblasts through PGC-1␣.

Differential expression of lipid metabolism-related genes and myosin heavy chain isoform genes in pig muscle tissue leading to different meat quality

“…As we expected, compared with the Landrace, the mRNA expression levels of MyHCI, MyHCIIa and MyHCIIx were greater, whereas the mRNA expression levels of MyHCIIb were lower in Rongchang pigs. Moreover, these results were further confirmed by the higher mRNA expression levels of PGC-1α in Rongchang pigs, because it is widely known that PGC-1α can induce myofiber-type transitions from fast to slow (Lin et al, 2002;Ueda et al, 2005;Yamaguchi et al, 2010). It is reported that MyHCIIb exhibits higher glycolytic metabolism capacity and glycogen content than other MyHC isoforms (Lefaucheur, 2010), and mainly uses glycogen and glucose as fuel through the glycolytic pathway.…”

PGC-1α Mediated Muscle Aerobic Adaptations to Exercise, Heat and Cold Exposure

“…This is inferred from recent studies that have demonstrated that heat stress may result in similar muscle adaptations to that observed following endurance exercise (Harris et al, 2003;Hooper, 1999;Liu & Brooks, 2012;Naylor et al, 2011;Yamaguchi et al, 2010). For instance, mild heat stress (39-40°C) has been shown to increase PGC-1α activity and induce PGC-1α mRNA and protein expression in a variety of muscle cell lines (Liu & Brooks, 2012;Yamaguchi et al, 2010), in addition to an increase in the mRNA content of key mitochondrial transcription factors (NRF1, NRF2 and Tfam), complex-IV subunits (COX2 and COX4) as well as glucose transporter 4 (GLUT4) mRNA (Liu & Brooks, 2012). In humans, heat exposure has shown to induce adaptations where PGC-1α may potentially be involved (Michael et al, 2001;Prior et al, 2004).…”

“…The production of metabolic heat during exercise appears to have a role in muscle oxidative phenotype transformations (Harris et al, 2003;Hooper, 1999;Liu & Brooks, 2012;Naylor et al, 2011;Yamaguchi et al, 2010). This is inferred from recent studies that have demonstrated that heat stress may result in similar muscle adaptations to that observed following endurance exercise (Harris et al, 2003;Hooper, 1999;Liu & Brooks, 2012;Naylor et al, 2011;Yamaguchi et al, 2010).…”

“…Although evidence suggests that elevations in muscle tissue temperature may influence muscle aerobic adaptations, much research is still needed to identify the signalling pathways involved (Harris et al, 2003;Liu & Brooks, 2012;Yamaguchi et al, 2010). Current evidence indicates that PGC-1α expression/activation and associated adaptations such as mitochondrial biogenesis and GLUT4 expression following heat stress may be via mechanisms involving NOS, SIRT1, and possibly AMPK signalling (Fig.…”

“…For instance, short term heat stress (30-45 min at 40-43°C) has shown to result in increased ROS formation and Ca 2+ leakage from sarcoplasmic reticulum in rat diaphragm and skeletal muscle fibres, respectively (van der Poel & Stephenson, 2007;Zuo et al, 2000). However, while both ROS and Ca 2+ are well known primary signals responsible for the induction/activation of PGC-1α and mitochondrial biogenesis, CaMKII, a downstream target of Ca 2+ , and; p38 MAPK, a downstream target of both ROS and Ca 2+ (Gomez-Cabrera et al, 2005;Irrcher et al, 2009;) have shown to not activate following heat treatment in vitro (Yamaguchi et al, 2010) and in vivo (Tamura et al, 2014). As such, it seems that CaMKII and p38 MAPK signalling are not involved in heat-induced PGC-1α mechanisms and ROS and Ca 2+ might act through AMPK-NOS pathways in up-regulating PGC-1α and mediating associated adaptations (Fig.…”