1. PUM2 aggravates the neuroinflammation and brain damage induced by ischemia–reperfusion through the SLC7A11-dependent inhibition of ferroptosis via suppressing the SIRT1
- Author
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Qingran Liu, Yongchang Liu, Yan Li, Zhen Hong, Shaoquan Li, and Chen Liu
- Subjects
Clinical Biochemistry ,Cell Biology ,General Medicine ,Molecular Biology - Abstract
Cerebral ischemia–reperfusion (I/R) injury occurs due to the restoration of blood perfusion after cerebral ischemia, which results in the damage of the brain structures and functions. Unfortunately, currently there are no effective methods for preventing and treating it. The pumilio 2 (PUM2) is a type of RBPs that has been reported to participate in the progression of several diseases. Ferroptosis is reported to be involved in I/R injury. Whether PUM2 modulated I/R injury through regulating ferroptosis remains to be elucidated. The cerebral I/R models including animal middle cerebral artery occlusion/reperfusion (MCAO/R) model and oxygen–glucose deprivation/reperfusion (OGD/R)-induced cortical neuron injury cell model of were established and, respectively. RT-qPCR was applied for evaluating PUM2, SIRT1 and SLC7A11 expression. Western blot was employed for measuring the protein expression levels. The viability of cortical neurons was tested by MTT assay. The histological damage of the brain tissues was assessed by H&E staining. The level of PUM2 was boosted in both the brain tissues of the MCAO model and OGD/R-induced cortical neuron injury model. Silence of PUM2 alleviated MCAO-induced brain injury and decreased the death of PC12 cell exposed to OGD/R. PUM2 also aggravated the accumulation of free iron in MCAO mice and OGD/R-induced cortical neuron injury model. In addition, PUM2 suppressed SLC7A11 via inhibiting expression of SIRT1. Rescue assays unveiled that downregulation of SLC7A11 reversed PUM2 mediated neuroinflammation and brain damage induced by I/R. PUM2 aggravated I/R-induced neuroinflammation and brain damage through the SLC7A11-dependent inhibition of ferroptosis by suppressing SIRT1, highlighting the role of PUM2 in preventing or treating cerebral I/R injury.
- Published
- 2022