Creatine and the Control of Myosin Synthesis in Differentiating Skeletal Muscle

Abstract

These experiments provide evidence that creatine, an end product of contraction unique to muscle, is involved in the control of muscle-protein synthesis. Skeletal muscle cells formed both in vitro and in vivo synthesize myosin, heavy chain faster when supplied creatine in vitro. The response is apparent within four hours after addition of creatine to the culture medium, and is dependent on concentration over a range of 10-100 MM creatine. The effect seems to be selective for cellspecific proteins(s), since the rate of total protein synthesis is unaffected.Since hypertrophy and atrophy of skeletal muscle result from increased and decreased muscular activity, one might postulate that a product of muscular activity stimulates contractile protein synthesis. Creatine is a likely candidate for such an effector, since it is a unique product of activity. We have investigated the possibility that creatine functions in this way by manipulating the external concentration of creatine available to differentiating skeletal muscle cells in vitro. We have found that increased concentrations of extracellular creatine selectively stimulates myosin heavy-chain synthesis. MATERIALS AND METHODS Skeletal

Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation

“…In the present study, we did not observe an increase in mean fiber area as previously reported, which could be because of our short period of supplementation compared with longer periods in studies showing this effect (94). Nonetheless, we did observe an early transcriptional and translational response at the cellular level, which explains previously observed effects of creatine supplementation on satellite cell proliferation and differentiation (16,36,41,63,93).…”

“…Indeed, we observed with CrM supplementation robust increases in p38 MAPK and PKBa mRNA and protein content, which are mandatory for myoblast differentiation and to enhance the expression of downstream myogenic differentiation markers, such as myogenin, myosin heavy chain, and caveolin-3, that may lead to muscle accretion (21). CrM supplementation increases actin and myosin protein and myosin mRNA content in vitro and myogenic transcription factors (MRF4, MEF2A, MEF2C, MEF2D, and myogenin) in vivo (41,102). We suggest that, taken together, the SPHK1-mediated pathways play an important role in CrM-mediated myoblast differentiation.…”

“…In vitro and in vivo, CrM supplementation alone (41,93) or in combination with progressive strength training or increased functional loading and compensatory hypertrophy (synergist ablation) (16) induces satellite cell (postnatal myogenic stem cells) proliferation and differentiation. This effect may be mediated, at least in part, by CrM-induced cell swelling, an early cellular response to CrM supplementation.…”

Effects of creatine supplementation on body mass and muscle girths in bodybuilders

“…This is suggestive of applying creatine supplementation for the purpose of reducing body fat content, which has not been frequent in the literature [11]. The available reports point to a wide range of creatine supplementation -from short, maximal exertions, to prolonged ones of low intensity [5,6,10,17,21]. Since the results are often equivocal, studies on creatine supplementation ought to be conducted on large groups and for long periods.…”

“…Administration of creatine augments the resynthesis of phosphocreatine in the muscles, especially following high-intensity exertions, which contributes to an improved work capacity and endurance, strength and muscle mass [2,6,7,13].…”