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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, 2021-04, Vol.47 (4), p.1, Article 61

COPYRIGHT 2021 Spandidos Publications ;COPYRIGHT 2021 Spandidos Publications ;Copyright Spandidos Publications UK Ltd. 2021 ;Copyright: © Li et al. 2021 ;ISSN: 1107-3756 ;EISSN: 1791-244X ;DOI: 10.3892/ijmm.2021.4894 ;PMID: 33649797

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Title:
miR‑335 promotes ferroptosis by targeting ferritin heavy chain 1 in in vivo and in vitro models of Parkinson's disease
Author: Li, Xinrong ; Si, Wenwen ; Li, Zhan ; Tian, Ye ; Liu, Xuelei ; Ye, Shanyu ; Huang, Zifeng ; Ji, Yichun ; Zhao, Caiping ; Hao, Xiaoqian ; Chen, Dongfeng ; Zhu, Meiling
Subjects: Analysis ; Animals ; Apoferritins - metabolism ; Apoptosis ; Cell growth ; Disease Models, Animal ; Dopamine ; Ferritin ; Ferroptosis - genetics ; Gene expression ; Homeostasis ; International economic relations ; Iron - metabolism ; Laboratory animals ; Lipid peroxidation ; Lipid Peroxidation - physiology ; Lipids ; Male ; Membrane Potential, Mitochondrial - physiology ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; Mutation ; Oxidopamine - toxicity ; Parkinson Disease - pathology ; Parkinsons disease ; Pathogenesis ; Phospholipid Hydroperoxide Glutathione Peroxidase - analysis ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species - metabolism ; Scientific equipment and supplies industry ; Surgery ; Tyrosine ; Tyrosine 3-Monooxygenase - analysis
Is Part Of: International journal of molecular medicine, 2021-04, Vol.47 (4), p.1, Article 61
Description: 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, and models of PD induced by 6‑OHDA were established. The results and 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 and 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 and models of PD, providing a potential therapeutic target for the treatment of PD.
Publisher: Greece: Spandidos Publications
Language: English
Identifier: ISSN: 1107-3756
EISSN: 1791-244X
DOI: 10.3892/ijmm.2021.4894
PMID: 33649797
Source: MEDLINE
Alma/SFX Local Collection
ProQuest Central

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miR‑335 promotes ferroptosis by targeting ferritin heavy chain 1 in in vivo and in vitro models of Parkinson's disease

COPYRIGHT 2021 Spandidos Publications ;COPYRIGHT 2021 Spandidos Publications ;Copyright Spandidos Publications UK Ltd. 2021 ;Copyright: © Li et al. 2021 ;ISSN: 1107-3756 ;EISSN: 1791-244X ;DOI: 10.3892/ijmm.2021.4894 ;PMID: 33649797

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