Inhibition of histone methyltransferase PRMT5 attenuates cisplatininduced hearing loss through the PI3K/Akt-mediated mitochondrial apoptotic pathway
作者机构：ENT Institute and Department of OtorhinolaryngologyEye&ENT HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceNHC Key Laboratory of Hearing Medicine(Fudan University)Fudan UniversityShanghai200031China Department of Otorhinolaryngology-Head and Neck SurgeryThe Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical UniversityWenzhou325000ZhejiangChina Department of Otolaryngology-Head and Neck SurgeryThe Third Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou510630China Department of OtolaryngologyShenzhen Institute of Translational MedicineShenzhen Second People's HospitalThe First Affiliated Hospital of Shenzhen UniversityShenzhen518035GuangdongChina
出 版 物：《Journal of Pharmaceutical Analysis》 (药物分析学报（英文版）)
年 卷 期：2023年第13卷第6期
页 面：590-602页
核心收录：
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
基 金：supported by grants from the National Natural Science Foundation of China(Grant Nos.:82271158,82192865,and 82071045) Wenzhou Municipal Science and Technology Research Program(Grant No.:2021Y0681)
主 题：Protein arginine methyltransferase 5 (PRMT5) LLY-283 Cisplatin Hearing loss Hair cell Spiral ganglion neuron
摘 要：This study aimed to evaluate the therapeutic potential of inhibiting protein arginine methyltransferase 5(PRMT5)in cisplatin-induced hearing *** effects of PRMT5 inhibition on cisplatin-induced auditory injury were determined using immunohistochemistry,apoptosis assays,and auditory brainstem *** mechanism of PRMT5 inhibition on hair cell survival was assessed using RNA-seq and Cleavage Under Targets and Tagment-quantitative polymerase chain reaction(CUT&Tag-qPCR)analyses in the HEI-OC1 cell *** inhibition of PRMT5 significantly alleviated cisplatin-induced damage to hair cells and spiral ganglion neurons in the cochlea and decreased apoptosis by protecting mitochondrial function and preventing the accumulation of reactive oxygen ***&Tag-qPCR analysis demonstrated that inhibition of PRMT5 in HEI-OC1 cells reduced the accumulation of H4R3me2s/H3R8me2s marks at the promoter region of the Pik3ca gene,thus activating the expression of *** findings suggest that PRMT5 inhibitors have strong potential as agents against cisplatininduced ototoxicity and can lay the foundation for further research on treatment strategies of hearing loss.
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