title: Distinct and additive effects of sodium bicarbonate and continuous mild heat stress on fiber type shift via calcineurin/NFAT pathway in human skeletal myoblasts.
abstract: Ingestion of sodium bicarbonate (NaHCO3) is known to enhance athletic performance, probably via increased extracellular buffering capacity. At present, little is known about the direct effects of NaHCO3 on myogenesis, especially in vitro. Here, we examined the effects of NaHCO3 and the combined effects of NaHCO3 and continuous mild heat stress (CMHS) at 39°C on the differentiation of human skeletal muscle myoblasts (HSMMs). Levels of myosin heavy chain (MyHC) type I mRNA increased with increasing NaHCO3 concentrations; in contrast, those of MyHC IIx decreased. The NaHCO3-induced fast-to-slow shift was additively enhanced by CMHS. Likewise, intracellular calcium levels and expression of three factors, nuclear factor of activated T cells c2 (NFATc2), NFATc4, and peroxisome-proliferator-activated receptor-γ coactivator-1α, were upregulated with increasing NaHCO3 concentrations; moreover, these effects of NaHCO3 were additively enhanced by CMHS. Overexpression experiments and small interfering RNA-mediated knockdown experiments confirmed that NFATc2 and NFATc4 were involved in MyHC I regulation. The present study provided evidence that NaHCO3 and CMHS distinctly and additively induced a fast-to-slow fiber type shift through changes in intracellular calcium levels and the modulation of calcium signaling.
authors.affiliation: Clinical Research Center, National Hospital Organization Sagamihara Hospital, Minami-ku, Sagamihara City, Kanagawa, Japan. tetsuo-yama@abeam.ocn.ne.jp
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Maiko
authors.initials: M
authors.lastname: Omori
authors.forename: Nobuho
authors.initials: N
authors.lastname: Tanaka
authors.forename: Naoshi
authors.initials: N
authors.lastname: Fukui
mesh_terms: D000293:Adolescent; D000328:Adult; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006358:Hot Temperature; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D032446:Myoblasts / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics*; D050778:NFATC Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D015398:Signal Transduction; D017693:Sodium Bicarbonate / Q000494:pharmacology*; D013312:Stress, Physiological; D014157:Transcription Factors / Q000096:biosynthesis; D015533:Transcriptional Activation; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D006360:Heat-Shock Proteins; D050778:NFATC Transcription Factors; C494003:NFATC1 protein, human; C494006:NFATC2 protein, human; C494008:NFATC3 protein, human; C494010:NFATC4 protein, human; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; D017693:Sodium Bicarbonate; D019703:Calcineurin; D018995:Myosin Heavy Chains; D002118:Calcium
keywords: calcium signaling; mild heat stress; myosin heavy chain; peroxisome proliferator-activated receptor-γ coactivator-1α; sodium bicarbonate