机构:[1]Traditional Chinese Medicine Innovation Research Center, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong 518104[2]Graduate School, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405深圳市中医院深圳医学信息中心[3]Guangdong Key Laboratory of Orthopedic Technology and Implant Materials, Key Laboratory of Trauma and Tissue Repair of Tropical Area of PLA, Hospital of Orthopedics, General Hospital of Southern Theater Command of PLA, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510010[4]Baoan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong 518101深圳市中医院深圳医学信息中心[5]Department of Anatomy, The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China
Parkinson's disease (PD) is a neurodegenerative disease characterized by the selective loss of dopaminergic neurons in the substantia nigra (SN). In a previous study, the authors demonstrated that ferritin heavy chain 1 (FTH1) inhibited ferroptosis in a model of 6-hydroxydopamine (6-OHDA)-induced PD. However, whether and how microRNAs (miRNAs/miRs) modulate FTH1 in PD ferroptosis is not yet well understood. In the present study, in vivo and in vitro models of PD induced by 6-OHDA were established. The results in vivo and in vitro revealed that the levels of the ferroptosis marker protein, glutathione peroxidase 4 (GPX4), and the PD marker protein, tyrosine hydroxylase (TH), were decreased in the model group, associated with a decreased FTH1 expression and the upregulation of miR-335. In both the in vivo and in vitro models, miR-335 mimic led to a lower FTH1 expression, exacerbated ferroptosis and an enhanced PD pathology. The luciferase 3 '-untranslated region reporter results identified FTH1 as the direct target of miR-335. The silencing of FTH1 in 6-OHDA-stimulated cells enhanced the effects of miR-335 on ferroptosis and promoted PD pathology. Mechanistically, miR-335 enhanced ferroptosis through the degradation of FTH1 to increase iron release, lipid peroxidation and reactive oxygen species (ROS) accumulation, and to decrease mitochondrial membrane potential (MMP). On the whole, the findings of the present study reveal that miR-335 promotes ferroptosis by targeting FTH1 in in vitro and in vivo models of PD, providing a potential therapeutic target for the treatment of PD.
基金:
Traditional Chinese Medicine Bureau of Guangdong Province, China [20203010]; Natural Science Foundation of Guangdong ProvinceNational Natural Science Foundation of Guangdong Province [2020A151501325]
第一作者机构:[1]Traditional Chinese Medicine Innovation Research Center, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong 518104[2]Graduate School, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405
共同第一作者:
通讯作者:
通讯机构:[1]Traditional Chinese Medicine Innovation Research Center, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong 518104[5]Department of Anatomy, The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China[*1]Department of Anatomy, The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, 232 Waihuan East Road, Guangzhou, Guangdong 510006, P.R. China[*2]Traditional Chinese Medicine Innovation Research Center, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, 3 Shajing Street, Baoan, Shenzhen, Guangdong 518104, P.R. China
推荐引用方式(GB/T 7714):
Li Xinrong,Si Wenwen,Li Zhan,et al.miR-335 promotes ferroptosis by targeting ferritin heavy chain 1 in in vivo and in vitro models of Parkinson's disease[J].INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE.2021,47(4):doi:10.3892/ijmm.2021.4894.
APA:
Li, Xinrong,Si, Wenwen,Li, Zhan,Tian, Ye,Liu, Xuelei...&Zhu, Meiling.(2021).miR-335 promotes ferroptosis by targeting ferritin heavy chain 1 in in vivo and in vitro models of Parkinson's disease.INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE,47,(4)
MLA:
Li, Xinrong,et al."miR-335 promotes ferroptosis by targeting ferritin heavy chain 1 in in vivo and in vitro models of Parkinson's disease".INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 47..4(2021)