TY - JOUR
AB - 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.
AD - Traditional Chinese Medicine Innovation Research Center, Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, Guangdong 518104, P.R. China
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, P.R. China
Baoan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Traditional Chinese Medicine, Shenzhen, Guangdong 518101, P.R. China
Graduate School, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China
Department of Anatomy, The Research Center of Basic Integrative Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, P.R. China
AU - Li,Xinrong
AU - Si,Wenwen
AU - Li,Zhan
AU - Tian,Ye
AU - Liu,Xuelei
AU - Ye,Shanyu
AU - Huang,Zifeng
AU - Ji,Yichun
AU - Zhao,Caiping
AU - Hao,Xiaoqian
AU - Chen,Dongfeng
AU - Zhu,Meiling
DA - 2021/04/01
DO - 10.3892/ijmm.2021.4894
IS - 4
JO - Int J Mol Med
KW - miR‑335
ferroptosis
ferritin heavy chain 1
Parkinson's disease
rat model
PY - 2021
SN - 1107-3756
1791-244X
SP - 61
ST - miR‑335 promotes ferroptosis by targeting ferritin heavy chain 1 in in vivo and in vitro models of Parkinson's disease
T2 - International Journal of Molecular Medicine
TI - miR‑335 promotes ferroptosis by targeting ferritin heavy chain 1 in in vivo and in vitro models of Parkinson's disease
UR - https://doi.org/10.3892/ijmm.2021.4894
VL - 47
ER -