Characterisation of intracellular molecular mechanisms modulated by carnosine in porcine myoblasts under basal and oxidative stress conditions

Citation

Palin, M.F., Lapointe, J., Gariépy, C., Beaudry, D., Kalbe, C. (2020). Characterisation of intracellular molecular mechanisms modulated by carnosine in porcine myoblasts under basal and oxidative stress conditions. PLoS ONE, [online] 15(9 September), http://dx.doi.org/10.1371/journal.pone.0239496

Plain language summary

Carnosine is a naturally occurring dipeptide present at high concentration in mammalian skeletal muscles. Carnosine was shown to affect muscle contraction, prevent the accumulation of oxidative metabolism by-products and help in maintaining the skeletal muscle pH. The present study was undertaken to gain additional knowledge about the intracellular mechanisms activated by carnosine in porcine muscle cells under basal and oxidative stress conditions. Study results demonstrated that carnosine acts differently in cells under oxidative stress and in basal condition. In fact, our results support a protective effect of carnosine against oxidative damage in porcine muscle cells, an effect that would be mediated through the p38 MAPK intracellular signaling pathway. The activation of the mTOR signaling pathway under basal condition also suggest a role for carnosine in cell proliferation, growth and survival.

Abstract

Carnosine is a naturally occurring histidine-containing dipeptide present at high concentration in mammalian skeletal muscles. Carnosine was shown to affect muscle contraction, prevent the accumulation of oxidative metabolism by-products and act as an intracellular proton buffer maintaining the muscle acid-base balance. The present study was undertaken to gain additional knowledge about the intracellular mechanisms activated by carnosine in porcine myoblast cells under basal and oxidative stress conditions. Satellite cells were isolated from the skeletal muscles of 3 to 4 day-old piglets to study the effect of 0, 10, 25 and 50 mM carnosine pre-treatments in cells that were exposed (0.3 mM H2O2) or not to an H2O2-induced oxidative stress. Study results demonstrated that carnosine acts differently in myoblasts under oxidative stress and in basal conditions, the only exception being with the reduction of reactive oxygen species and protein carbonyls observed in both experimental conditions with carnosine pre-treatment. In oxidative stress conditions, carnosine pre-treatment increased the mRNA abundance of the nuclear factor, erythroid 2 like 2 (NEF2L2) transcription factor and several of its downstream genes known to reduce H2O2. Carnosine prevented the H2O2-mediated activation of p38 MAPK in oxidative stress conditions, whereas it triggered the activation of mTOR under basal conditions. Current results support the protective effect of carnosine against oxidative damage in porcine myoblast cells, an effect that would be mediated through the p38 MAPK intracellular signaling pathway. The activation of the mTOR signaling pathway under basal condition also suggest a role for carnosine in myoblasts proliferation, growth and survival.