Baicalein Inhibits Cerebral Ischemia-Reperfusion Injury through SIRT6-Mediated FOXA2 Deacetylation to Promote SLC7A11 Expression

被引:1
|
作者
Fang, Cuini [1 ]
Liu, Xirong [1 ]
Zhang, Fuxiu [1 ]
Song, Tao [1 ]
机构
[1] Hunan Normal Univ, Affiliated Hosp 1, Hunan Prov Peoples Hosp, Changsha 410000, Hunan, Peoples R China
基金
湖南省自然科学基金;
关键词
cerebral ischemia-reperfusion injury; FOXA2; ferroptosis; SIRT6; SLC7A11; SIRTUIN; 6; FERROPTOSIS; BRAIN;
D O I
10.1523/ENEURO.0174-24.2024
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Ischemic stroke (IS) poses a serious threat to patient survival. The inhibition of ferroptosis can effectively alleviate ischemia-reperfusion (I/R) injury, suggesting potential targets in the ferroptosis pathway for the treatment of IS. In this study, MCAO/R mice and OGD/R-induced HT22 cell were constructed. It was found that baicalein decreased ROS, MDA, and Fe2+ levels, upregulated GSH levels, and enhanced the expression of ferroptosis-related proteins (GPX4 and SLC7A11), downregulated the expression of proapoptotic proteins (Bax, cytochrome c, and cleaved caspase-3), and upregulated the expression of an antiapoptotic protein (Bcl-2), ameliorating cerebral I/R injury. In animal and cell models, Sirtuin6 (SIRT6) is downregulated, and Forkhead boxA2 (FOXA2) expression and acetylation levels are abnormally upregulated. SIRT6 inhibited FOXA2 expression and acetylation. Baicalein promoted FOXA2 deacetylation by upregulating SIRT6 expression. FOXA2 transcriptionally inhibits SLC7A11 expression. In conclusion, baicalein inhibited apoptosis and partially suppressed the role of ferroptosis to alleviate cerebral I/R injury via SIRT6-mediated FOXA2 deacetylation to promote SLC7A11 expression.
引用
收藏
页数:14
相关论文
共 50 条
  • [21] Research Paper Nrf2 inhibits ferroptosis and protects against acute lung injury due to intestinal ischemia reperfusion via regulating SLC7A11 and HO-1
    Dong, Hui
    Qiang, Zhuanzhuan
    Chai, Dongdong
    Peng, Jiali
    Xia, Yangyang
    Hu, Rong
    Jiang, Hong
    AGING-US, 2020, 12 (13): : 12943 - 12959
  • [22] PUM2 aggravates the neuroinflammation and brain damage induced by ischemia-reperfusion through the SLC7A11-dependent inhibition of ferroptosis via suppressing the SIRT1
    Liu, Qingran
    Liu, Yongchang
    Li, Yan
    Hong, Zhen
    Li, Shaoquan
    Liu, Chen
    MOLECULAR AND CELLULAR BIOCHEMISTRY, 2023, 478 (03) : 609 - 620
  • [23] Protective Effect of Compound Tongluo Decoction on Brain Vascular Endothelial Cells after Ischemia-Reperfusion by Inhibition of Ferroptosis Through Regulating Nrf2/ARE/SLC7A11 Signaling Pathway
    Li, Peiyi
    Wang, Zhongda
    Zhao, Tong
    Cheng, Xiaolan
    Zhang, Zhennian
    Wang, Jingqing
    Wang, Sulei
    Huang, Ruiou
    Hui, Zhen
    ADVANCED BIOLOGY, 2024, 8 (03):
  • [24] Pentoxifylline protects against cerebral ischaemia-reperfusion injury through ferroptosis regulation via the Nrf2/SLC7A11/GPX4 signalling pathway
    Li, Pei
    Chen, Jun -Min
    Ge, Shi-Hao
    Sun, Mei-Lin
    Lu, Jun-Dong
    Liu, Fan
    Wang, Le -Le
    Zhang, Xin
    Wang, Xiao-Peng
    EUROPEAN JOURNAL OF PHARMACOLOGY, 2024, 967
  • [25] Electroacupuncture protects against cerebral ischemia-reperfusion injury via regulating P2x7R expression
    Chen, Sijia
    Zhu, Ye
    Lin, Feihong
    Jiang, Hanming
    Liu, Haipeng
    Li, Shan
    Huang, Xuliang
    Mo, Yunchang
    Wang, Junlu
    Dai, Qinxue
    CEREBRAL CIRCULATION-COGNITION AND BEHAVIOR, 2025, 8
  • [26] USP38 exacerbates myocardial injury and malignant ventricular arrhythmias after ischemia/reperfusion by promoting ferroptosis through the P53/SLC7A11 pathway
    Gong, Yang
    Yang, Hongjie
    Chen, Tao
    Zhang, Jingjing
    Kong, Bin
    Shuai, Wei
    Huang, He
    INTERNATIONAL IMMUNOPHARMACOLOGY, 2025, 145
  • [27] Fat mass and obesity-associated protein alleviates cerebral ischemia/ reperfusion injury by inhibiting ferroptosis via miR-320-3p/SLC7A11 axis
    Peng, Qiang
    Deng, Yang
    Xu, Zhaohan
    Duan, Rui
    Wang, Wei
    Wang, Shiyao
    Hong, Ye
    Wang, Qingguang
    Zhang, Yingdong
    BIOCHEMICAL PHARMACOLOGY, 2024, 230
  • [28] MiR-93 INHIBITS MYOCARDIAL APOPTOSIS IN RATS WITH MYOCARDIAL ISCHEMIA-REPERFUSION INJURY THROUGH REGULATING Mfn2 EXPRESSION
    Zhu, Z-D
    Chem, Y-F
    Shi, H-M
    JOURNAL OF BIOLOGICAL REGULATORS AND HOMEOSTATIC AGENTS, 2020, 34 (03): : 909 - 916
  • [29] GATA6 Inhibits Neuronal Autophagy and Ferroptosis in Cerebral ischemia-reperfusion Injury Through a miR-193b/ATG7 axis-dependent Mechanism
    Fan, Weijian
    Rong, Jianjie
    Shi, Weihao
    Liu, Wei
    Wang, Jie
    Tan, Jinyun
    Yu, Bo
    Tong, Jindong
    NEUROCHEMICAL RESEARCH, 2023, 48 (08) : 2552 - 2567
  • [30] GATA6 Inhibits Neuronal Autophagy and Ferroptosis in Cerebral ischemia-reperfusion Injury Through a miR-193b/ATG7 axis-dependent Mechanism
    Weijian Fan
    Jianjie Rong
    Weihao Shi
    Wei Liu
    Jie Wang
    Jinyun Tan
    Bo Yu
    Jindong Tong
    Neurochemical Research, 2023, 48 : 2552 - 2567