DBDPE inhibits myogenic differentiation of C2C12 cells through inhibiting mitochondrial function and PI3K/AKT/mTOR...

In recent years, decabromodiphenyl ethane (DBDPE), a type of brominated flame retardant, has gained popularity in industry as an alternative to decabromodiphenyl ether (BDEs). However, DBDPE exposure poses environmental pollution and primarily impacts muscle contraction and the reproductive endocrine system. The cellular implications and underlying mechanisms of DBDPE's effects on muscle remain poorly understood. In the present study, we investigated the effect of DBDPE on myoblast differentiation, apoptosis, as well as the potential mechanisms involved. The results demonstrated that exposure to DBDPE disrupted the differentiation of myotubes, inhibited cell proliferation, and increased levels of reactive oxygen species (ROS), ultimately leading to cell death. In addition, the RNAseq analysis revealed that DBDPE mainly affected the biological processes in mitochondria related to oxidative phosphorylation, ATP synthesis coupled electron transport, etc. Then we demonstrated that DBDPE inhibited mitochondrial membrane potential and ATP production, implying DBDPE resulted in mitochondrial dysfunction in C2C12 cells. Mechanistically, we showed that PI3K/AKT/mTOR signaling pathway was inhibited by DBDPE in C2C12 cells. And the apoptosis rate was significantly increased by DBDPE as demonstrated by increased active caspase-3 and TUNEL signal. Taken together, these findings suggest that low-dose exposure to DBDPE hampers myogenic differentiation and mitochondrial function, and increased cellular apoptosis through PI3K/AKT/mTOR signaling pathway, providing important insights for understanding its environmental toxic effects and conducting risk assessments.