Autophagy promotes neuronal ferroptosis by degrading ferritin and induces early brain injury after subarachnoid hemorrhage in rats

Yidan LIANG; Wang QIN; Hao HUANG; Yuanjun XIN; Jun ZHAO; Xiang XIANG; Xintong WU; Zhaohui HE

doi:10.16016/j.1000-5404.201902124

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Autophagy promotes neuronal ferroptosis by degrading ferritin and induces early brain injury after subarachnoid hemorrhage in rats

更新时间：2026-01-09

- Autophagy promotes neuronal ferroptosis by degrading ferritin and induces early brain injury after subarachnoid hemorrhage in rats
- Journal of Third Military Medical University Vol. 41, Issue 15, Pages: 1407-1414(2019)
- 作者机构：
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81870927)
- DOI：10.16016/j.1000-5404.201902124
  CLC：
- Received：25 February 2019，
  
  Published：15 August 2019
- 稿件说明：
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Yidan LIANG, Wang QIN, Hao HUANG, et al. Autophagy promotes neuronal ferroptosis by degrading ferritin and induces early brain injury after subarachnoid hemorrhage in rats[J]. Journal of Third Military Medical University, 2019, 41(15): 1407-1414.
DOI：

Yidan LIANG, Wang QIN, Hao HUANG, et al. Autophagy promotes neuronal ferroptosis by degrading ferritin and induces early brain injury after subarachnoid hemorrhage in rats[J]. Journal of Third Military Medical University, 2019, 41(15): 1407-1414. DOI： 10.16016/j.1000-5404.201902124.

摘要

Abstract

Objective

To determine the effect of suppressing autophagy on the recovery of early brain injury (EBI) after subarachnoid hemorrhage (SAH) in rats

and to reveal the mechanism in which autophagy promotes neuronal ferroptosis and then affects EBI.

Methods

SD rats were randomly divided into control group

SAH group

SAH+LV-ATG5 group and SAH+LV-Scramble group

with 12 animals in each group. Rat model of SAH were established by intravascular puncture. Lentiviral vector LV-ATG5 targeting autophagy-related gene 5 (ATG5) was constructed to inhibit autophagy. Immunofluorescence assay was used to detect the expression and location of ATG5

ferritin heavy polypeptide 1 (FTH1) and glutathione peroxidase 4 (GPX4) in neurons in 24 h after SAH establishment. The mRNA expression of ATG5 was detected by PCR

and the protein expression of ATG5

LC3Ⅱ/Ⅰ

FTH1 and GPX4 were detected by Western blotting. The changes of neuronal morphology and function were detected by Nissl staining

and neurological score and brain water content were also detected. Intracellular iron deposition

iron content

malonaldehyde (MDA) content and GPX4 activity were measured to evaluate the ferroptosis.

Results

Immunofluorescence assay showed that ATG5

FTH1 and GPX4 were widely expressed in the cytoplasm of cortical neurons after SAH. The results of PCR and Western blotting indicated that the expression of ATG5 at mRNA and protein levels

and LC3Ⅱ/Ⅰ at protein level was significantly decreased (

0.05)

and autophagy was successfully inhibited. When autophagy was inhibited

Nissl staining showed improvements on neuronal morphology and function

neurological function score was improved (

0.05)

and brain water content was decreased (

0.05). Western blot assay indicated that the expression le

vels of FTH1 and GPX4 were decreased after SAH (

0.05)

however

the levels were increased when autophagy was inhibited (

0.05). Furthermore

autophagy inhibition also reduced iron deposition

and cellular labile iron and MDA contents (

0.05)

and also elevated GSH content and GPX4 activity (

0.05).

Conclusion

Autophagy may promote neuronal ferroptosis by degrading ferritin

result in cellular labile iron increase

and finally early brain injury.

关键词

Keywords

references

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