Paeonol inhibits the progression of intracerebral haemorrhage by mediating the HOTAIR/UPF1/ACSL4 axis
| Autor: | Wen-Ying Gao, Zheng-Long Jin, Shang-Zhen Yu, Qing Shi, Ye-Feng Cai, Tao Yu, Shao-Jun Liao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Neurosciences. Biological psychiatry. Neuropsychiatry 03 medical and health sciences chemistry.chemical_compound ACSL4 Mice 0302 clinical medicine In vivo Coenzyme A Ligases Animals Humans MTT assay Viability assay cardiovascular diseases Cerebral Hemorrhage Neurons Original Paper ICH General Neuroscience Acetophenones HOTAIR Glutathione In vitro ferroptosis nervous system diseases Blot Mice Inbred C57BL 030104 developmental biology paeonol HEK293 Cells chemistry UPF1 Cancer research Trans-Activators RNA Long Noncoding Neurology (clinical) Paeonol 030217 neurology & neurosurgery RC321-571 cell injury |
| Zdroj: | ASN NEURO ASN Neuro, Vol 13 (2021) |
| ISSN: | 1759-0914 |
| Popis: | Intracerebral haemorrhage (ICH) is a devastating subtype of stroke with high morbidity and mortality. It has been reported that paeonol (PAN) inhibits the progression of ICH. However, the mechanism by which paeonol mediates the progression of ICH remains unclear. To mimic ICH in vitro, neuronal cells were treated with hemin. An in vivo model of ICH was established to detect the effect of paeonol on ferroptosis in neurons during ICH. Cell viability was tested by MTT assay. Furthermore, cell injury was detected by GSH, MDA and ROS assays. Ferroptosis was examined by iron assay. RT-qPCR and western blotting were used to detect gene and protein expression, respectively. The correlation among HOTAIR, UPF1 and ACSL4 was explored by FISH, RNA pull-down and RIP assays. Paeonol significantly inhibited the ferroptosis of neurons in ICH mice. In addition, paeonol significantly reversed hemin-induced injury and ferroptosis in neurons, while this phenomenon was notably reversed by HOTAIR overexpression. Moreover, paeonol notably inhibited ferroptosis in hemin-treated neuronal cells via inhibition of ACSL4. Additionally, HOTAIR bound to UPF1, and UPF1 promoted the degradation of ACSL4 by binding to ACSL4. Furthermore, HOTAIR overexpression reversed paeonol-induced inhibition of ferroptosis by mediating the UPF1/ACSL4 axis. Paeonol inhibits the progression of ICH by mediating the HOTAIR/UPF1/ACSL4 axis. Therefore, paeonol might serve as a new agent for the treatment of ICH. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|