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
  • [41] PUM2 aggravates the neuroinflammation and brain damage induced by ischemia–reperfusion through the SLC7A11-dependent inhibition of ferroptosis via suppressing the SIRT1
    Qingran Liu
    Yongchang Liu
    Yan Li
    Zhen Hong
    Shaoquan Li
    Chen Liu
    Molecular and Cellular Biochemistry, 2023, 478 : 609 - 620
  • [42] Glycosides of Buyang Huanwu decoction inhibits pyroptosis associated with cerebral ischemia-reperfusion through Nrf2-mediated antioxidant signaling pathway both in vivo and in vitro
    She, Yan
    Shao, Le
    Jiao, Keyan
    Sun, Ruiting
    Lang, Ting
    Long, Hongping
    Tang, Yinghong
    Zhang, Wei
    Ding, Changsong
    Deng, Changqing
    PHYTOMEDICINE, 2023, 120
  • [43] Astragaloside IV Alleviates Cerebral Ischemia-Reperfusion Injury through NLRP3 Inflammasome-Mediated Pyroptosis Inhibition via Activating Nrf2
    Xiao, Lan
    Dai, Ziwei
    Tang, Wenjing
    Liu, Canwen
    Tang, Biao
    OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2021, 2021
  • [44] Diosmetin alleviates cerebral ischemia-reperfusion injury through Keap1-mediated Nrf2/ARE signaling pathway activation and NLRP3 inflammasome inhibition
    Shi, Min
    Wang, Jianqiang
    Bi, Fangfang
    Bai, Zhangyong
    ENVIRONMENTAL TOXICOLOGY, 2022, 37 (06) : 1529 - 1542
  • [45] Rutaecarpine may improve neuronal injury, inhibits apoptosis, inflammation and oxidative stress by regulating the expression of ERK 1/2 and Nrf2/HO-1 pathway in rats with cerebral ischemia-reperfusion injury
    Han, Meiyu
    Hu, Lin
    Chen, Yang
    DRUG DESIGN DEVELOPMENT AND THERAPY, 2019, 13 : 2923 - 2931
  • [46] MicroRNA-497 promotes proliferation and inhibits apoptosis of cardiomyocytes through the downregulation of Mfn2 in a mouse model of myocardial ischemia-reperfusion injury (Publication with Expression of Concern)
    Qin, Lei
    Yang, Wen
    Wang, Yao-Xin
    Wang, Zhen-Jun
    Li, Chen-Chen
    Li, Man
    Liu, Jie-Yun
    BIOMEDICINE & PHARMACOTHERAPY, 2018, 105 : 103 - 114
  • [47] Overexpressed CD73 attenuates GSDMD-mediated astrocyte pyroptosis induced by cerebral ischemia-reperfusion injury through the A2B/ NF-κB pathway
    Zhuang, Hao
    Lei, Wen
    Wu, Qiang
    Zhao, Songyun
    Zhao, Yunxuan
    Zhang, Shizhe
    Zhao, Ning
    Sun, Jun
    Liu, Yuankun
    EXPERIMENTAL NEUROLOGY, 2025, 386
  • [48] m6A methyltransferase METTL3 promotes oral squamous cell carcinoma progression through enhancement of IGF2BP2-mediated SLC7A11 mRNA stability
    Xu, Le
    Li, Qingdang
    Wang, Yifei
    Wang, Lin
    Guo, Yuxing
    Yang, Rong
    Zhao, Na
    Ge, Na
    Wang, Yixiang
    Guo, Chuanbin
    AMERICAN JOURNAL OF CANCER RESEARCH, 2021, 11 (11): : 5282 - +
  • [49] Buyang huanwu decoction inhibits the activation of the RhoA/Rock2 signaling pathway through the phenylalanine metabolism pathway, thereby reducing neuronal apoptosis following cerebral ischemia-reperfusion injury
    Li, Yanling
    Hu, Zhongji
    Xie, Linli
    Xiong, Tingting
    Zhang, Yanyan
    Bai, Yang
    Ding, Huang
    Huang, Xiaoping
    Liu, Xiaodan
    Deng, Changqing
    JOURNAL OF ETHNOPHARMACOLOGY, 2025, 340
  • [50] Shaoyao-Gancao Decoction Promoted Microglia M2 Polarization via the IL-13-Mediated JAK2/STAT6 Pathway to Alleviate Cerebral Ischemia-Reperfusion Injury
    Lu, Juanjuan
    Wang, Jie
    Yu, Long
    Cui, Rong
    Zhang, Ying
    Ding, Hanqing
    Yan, Guofeng
    MEDIATORS OF INFLAMMATION, 2022, 2022