Taurine Protects C2C12 Myoblasts From Impaired Cell Proliferation and Myotube Differentiation Under Cisplatin-Induced ROS Exposure

Abstract

In cancer patients, chemotherapeutic medication induces aberrant ROS (reactive oxygen species) accumulation in skeletal muscles, resulting in myofiber degradation, muscle weakness, and even cachexia, which further leads to poor therapeutic outcomes. Acting as an antioxidant, taurine is extensively used to accelerate postexercise muscle recovery in athletes. The antioxidant effects of taurine have been shown in mature myotubes and myofibers but not yet in myoblasts, the myotube precursor. The proliferation and differentiation ability of myoblasts play a very important role in myofiber repair and regeneration, which is usually impaired during chemotherapeutics in cancer patients as well. Here, we explored the effects of taurine supplementation on C2C12 myoblasts exposed to cisplatin-induced ROS. We found that cisplatin treatment led to dramatically decreased cell viability; accumulated ROS level; down-regulated expressions of MyoD1 (myoblast determination protein 1), myogenin, and MHC (myosin heavy chain); and impaired myotube differentiation in myoblasts. Significantly, taurine supplementation protected myoblasts against cisplatin-induced cell viability decrease, promoted cellular ROS clearance, and, most importantly, preserved the expressions of MyoD1, myogenin, and MHC as well as myotube differentiation ability. We further conducted NMR-based metabolomic analysis to clarify the underlying molecular mechanisms. We identified 14 characteristic metabolites primarily responsible for the discrimination of metabolic profiles between cisplatin-treated cells and normal counterparts, including increased levels of BCAAs (branched-chain amino acids: leucine and isoleucine), alanine, glycine, threonine, glucose, ADP (adenosine diphosphate), phenylalanine, and PC (O-phosphocholine), and decreased levels of lysine, β-alanine, choline, GPC (sn-glycero-3-phosphocholine), and myo-inositol. Evidently, taurine supplementation partially reversed the changing trends of several metabolites (isoleucine, threonine, glycine, PC, β-alanine, lysine, and myo-inositol). Furthermore, taurine supplementation promoted the proliferation and myotube differentiation of myoblasts by alleviating cellular catabolism, facilitating GSH (reduced glutathione) biosynthesis, improving glucose utilization and TCA (tricarboxylic acid) cycle anaplerosis, and stabilizing cellular membranes. Our results demonstrated the protective effects of taurine on cisplatin-impaired myoblasts and elucidated the mechanistic rationale for the use of taurine to ameliorate muscle toxicity in clinical chemotherapy cancer patients.

NMR-Based Metabolomic Analysis for the Effects of Trimethylamine N-Oxide Treatment on C2C12 Myoblasts under Oxidative Stress

“…The essential precursors of PPC are choline and PC, and the decomposition product of PPC is GPC [ 41 ]. Upon lipid peroxidation destroying lipid membranes, the promotion of PPC synthesis is a prerequisite for maintaining membrane integrity [ 24 ]. Compared with the normal group, the H 2 O 2 group displayed the increased level of PC, and basically unchanged levels of choline and GPC.…”

“…To measure the cell viability, C2C12 cells were seeded in 96-well plates and cultured as previously described [ 24 ]. Then, 20 μL of the solution used in the CellTiter 96 AQueous One Solution Cell Proliferation Assay Kit (MTS, Promega, Madison, WI, USA) was added to each well.…”

Taurine stimulates protein synthesis and proliferation of C2C12 myoblast cells through the PI3K-ARID4B-mTOR pathway

“…Tau can attenuate skeletal muscle injury induced by diquat toxicity (28) . Recent reports have found that Tau can promote proliferation and protein synthesis of muscle cells through attenuating catabolic processes (29,30) . These above reports point out that Tau is a key regulator of protein synthesis and proliferation of muscle cells.…”

Satellite Cells Exhibit Decreased Numbers and Impaired Functions on Single Myofibers Isolated from Vitamin B6-Deficient Mice

“…Lysine deficiency was found to induce apoptosis in the satellite cells isolated from the muscles of piglets, and lysine supplementation promoted satellite cell proliferation via the mTORC1 pathway [45,46]. Moreover, a recent study demonstrated that taurine supplementation can increase the viability of C2C12 cells that have been exposed to reactive oxygen species (ROS) as well as promote their proliferation and differentiation [47]. Branched-chain amino acid aminotransferase, an enzyme involved in the catabolism of branched-chain amino acids, is essential for maintaining the self-renewal of mouse embryonic stem cells [48].…”