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Cyclic Stretch Facilitates Myogenesis in C2C12 Myoblasts and Rescues Thiazolidinedione-Inhibited Myotube Formation.

ABSTRACT: Thiazolidinedione (TZD), a specific peroxisome proliferator-activated receptor ? (PPAR?) agonist, was developed to control blood glucose in diabetes patients. However, several side effects were reported that increased the risk of heart failure. We used C2C12 myoblasts to investigate the role of PPARs and their transcriptional activity during myotube formation. The role of mechanical stretch during myogenesis was also explored by applying cyclic stretch to the differentiating C2C12 myoblasts with 10% strain deformation at 1?Hz. The myogenesis medium (MM), composed of Dulbecco's modified Eagle's medium with 2% horse serum, facilitated myotube formation with increased myosin heavy chain and ?-smooth muscle actin (?-SMA) protein expression. The PPAR? protein and PPAR response element (PPRE) promoter activity decreased during MM induction. Cyclic stretch further facilitated the myogenesis in MM with increased ?-SMA and decreased PPAR? protein expression and inhibited PPRE promoter activity. Adding a PPAR? agonist (TZD) to the MM stopped the myogenesis and restored the PPRE promoter activity, whereas a PPAR? antagonist (GW9662) significantly increased the myotube number and length. During the myogenesis induction, application of cyclic stretch rescued the inhibitory effects of TZD. These results provide novel perspectives for mechanical stretch to interplay and rescue the dysfunction of myogenesis with the involvement of PPAR? and its target drugs.

SUBMITTER: Chang YJ

PROVIDER: S-EPMC4800178 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Cyclic Stretch Facilitates Myogenesis in C2C12 Myoblasts and Rescues Thiazolidinedione-Inhibited Myotube Formation.

Chang Ya-Ju YJ Chen Yun-Ju YJ Huang Chia-Wei CW Fan Shih-Chen SC Huang Bu-Miin BM Chang Wen-Tsan WT Tsai Yau-Sheng YS Su Fong-Chin FC Wu Chia-Ching CC

Frontiers in bioengineering and biotechnology 20160321

Thiazolidinedione (TZD), a specific peroxisome proliferator-activated receptor γ (PPARγ) agonist, was developed to control blood glucose in diabetes patients. However, several side effects were reported that increased the risk of heart failure. We used C2C12 myoblasts to investigate the role of PPARs and their transcriptional activity during myotube formation. The role of mechanical stretch during myogenesis was also explored by applying cyclic stretch to the differentiating C2C12 myoblasts with ...[more]

PMID: 27047938

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Project description: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.

Dataset Information

Cyclic Stretch Facilitates Myogenesis in C2C12 Myoblasts and Rescues Thiazolidinedione-Inhibited Myotube Formation.

Publications

Cyclic Stretch Facilitates Myogenesis in C2C12 Myoblasts and Rescues Thiazolidinedione-Inhibited Myotube Formation.

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