摘要
Dexamethasone is a common glucocorticoid medication with adverse effects that can cause muscle atrophy,but no drug intervention has been approved or recommended for this condition.KF-8 is a rice bran-derived anti-oxidant peptide that extends the lifespan of Caenorhabditis elegans.We established a C.elegans model of dexamethasone-induced myopathy to evaluate the potential therapeutic effects of KF-8 in this model.C.elegans muscle function was assessed in terms of locomotory behaviors including crawling,swimming,burrowing,pharyngeal pumping,and head swing.Muscle actin filament integrity was evaluated using fluorescence imaging.The molecular mechanisms of KF-8 were investigated using transcriptome sequencing,quantitative real-time PCR(qRT-PCR),RNA interference,and Western blot analysis.Dexamethasone disrupted actin filaments in the striated muscles of the body wall and inhibited C.elegans crawling,swimming,burrowing,pharyngeal pumping,and head swing.KF-8 reversed the actin filament disruption and locomotor dysfunction induced by dexamethasone.Transcriptome sequencing,pathway enrichment,and qRT-PCR analyses revealed that KF-8 regulated the locomotion-related genes W04G5.10,vha-12,and ddr-1,as well as age-1(the catalytic subunit ortholog of phosphatidylinositol 3-kinase(PI3K)),and akt1.RNA interference,conducted using a genetically engineered Escherichia coli HT115 strain as a food source,confirmed age-1 as a key regulator of locomotor function of C.elegans.Further mechanistic studies with C2C12 myotubes showed that KF-8 regulated the IRS-PI3K-Akt pathway,the master regulator of protein synthesis and degradation.Together,these findings suggest that KF-8 protects against dexamethasoneinduced myopathy in C.elegans by regulating locomotion-related genes and the IRS-PI3K-Akt pathway.
基金
supported by funding from the National Key Research and Development Program of China(2022YFF1100203)
National Natural Science Foundation of China(32372349)
Science and Technology Innovation Talent Project of Hunan Province(2022RC3056)
Key Research and Development Program of Hunan Province(2024AQ2020)。
