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-oxid...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.展开更多
基金supported by funding from the National Key Research and Development Program of China(2022YFF1100203)National Natural Science Foundation of China(32372349)+1 种基金Science and Technology Innovation Talent Project of Hunan Province(2022RC3056)Key Research and Development Program of Hunan Province(2024AQ2020)。
文摘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.
