Involvement of the STAT3/HIF-1α signaling pathway in α-synuclein-induced ferroptosis

被引：1
作者：
Zhang, Han [1 ,5 ]
Zhang, Jieli [1 ]
Jing, Xiuna [2 ,3 ]
Huang, Kaixun [1 ]
Chen, Ying [2 ,3 ]
Shen, Qingyu [2 ,3 ]
Tao, Enxiang [1 ,2 ,3 ,4 ]
Lin, Danyu [1 ]
机构：
[1] Sun Yat Sen Univ, Affiliated Hosp 8, Dept Neurol, Shenzhen, Peoples R China
[2] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Dept Neurol, Guangzhou, Peoples R China
[3] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou, Peoples R China
[4] Sun Yat Sen Univ, Zhongshan Sch Med, Guangdong Prov Key Lab Brain Funct & Dis, Guangzhou, Peoples R China
[5] Southern Med Univ, Nanfang Hosp, Dept Neurol, Guangzhou, Peoples R China
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2025年 / 752卷
关键词：
Parkinson's disease; alpha-synuclein; Ferroptosis; STAT3/HIF-1; alpha; Transcriptomics;
D O I：
10.1016/j.bbrc.2025.151419
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Oligomeric alpha-synuclein (alpha-syn) aggregates, which are a critical pathological feature of Parkinson's disease (PD), can induce neuroinflammation and neurodegeneration. Our previous study revealed a decrease in IL6ST/JAK2/ STAT3/HIF-1 alpha pathway in alpha-syn-induced microglia. As we all know, the JAK2/STAT3 signaling pathway is essential for modulating inflammation, controlling cell growth and exhibiting antiapoptotic responses. However, the precise role of STAT3/HIF-1 alpha in the ferroptosis of alpha-syn pathology has not been identified in vivo. In this study, above all, we successfully established alpha-syn-induced mouse models of Parkinson's disease. Our immunohistochemistry results demonstrated that alpha-syn could activate IL6ST/STAT3/HIF-1 alpha pathway in a model of alpha-syn-induced PD. We further conducted transcriptomic analysis on a mouse model of alpha-syn-induced PD, and GSEA revealed an association with ferroptosis. Consequently, we focused on investigating how alpha-syn might regulate the transcriptional activation of HSPB1. In conclusion, we determined the relationship between ferroptosis and the STAT3/HIF-1 alpha pathway in alpha-syn-related pathology in vivo. Oligomeric alpha-syn could induce ferroptosis via the STAT3/HIF-1 alpha signaling pathway.
引用
收藏
页数：11
相关论文
共 50 条
[21]   Cardamonin Attenuates Myocardial Ischemia/ Reperfusion-Induced Ferroptosis Through Promoting STAT3 Signaling [J].
Yang, Tao ;
Wu, Pengcui ;
Jiang, Luping ;
Chen, Ran ;
Jin, Qiao ;
Ye, Guohong .
JOURNAL OF INFLAMMATION RESEARCH, 2024, 17 :8861-8879
[22]   LSD1 inhibition by tranylcypromine hydrochloride reduces alkali burn-induced corneal neovascularization and ferroptosis by suppressing HIF-1α pathway [J].
Deng, Qian ;
Gao, Yuelan ;
Wang, Yujin ;
Mao, Jiewen ;
Yan, Yulin ;
Yang, Zixian ;
Cong, Yuyu ;
Yang, Yanning ;
Wan, Shanshan .
FRONTIERS IN PHARMACOLOGY, 2024, 15
[23]   Silencing of LOX-1 attenuates high glucose-induced ferroptosis in THVECs via the HIF-1α/SLC7A11 signaling pathway [J].
Zhang, Haiqi ;
Chang, Xinying ;
Liu, Xuan ;
Zhang, Baozhuan ;
Wang, Rongrong ;
Wang, Yuhui ;
Dai, Simeng ;
Yao, Tonghan ;
Zhang, Qi .
EXPERIMENTAL CELL RESEARCH, 2025, 446 (02)
[24]   Astaxanthin Prevents Glucocorticoid-Induced Femoral Head Osteonecrosis by Targeting Ferroptosis through the JAK2/STAT3 Signaling Pathway [J].
Lin, Yu-zhe ;
Chen, Zi-hao ;
Yang, Jian-feng ;
Han, Li-jiang ;
Yu, Yi-tian ;
Zhan, Juan-nan ;
Tan, Guang-chan ;
Liu, Le-yang ;
Xie, Cheng-long ;
Shan, Ping ;
Jin, Chen ;
Liu, Hai-xiao .
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2025, 73 (07) :4270-4287
[25]   HIF-1α and STAT3 client proteins interacting with the cancer chaperone Hsp90 -: Therapeutic considerations [J].
Kim, Hanna Leah ;
Cassone, Marco ;
Otvos, Laszlo, Jr. ;
Vogiatzi, Paraskevi .
CANCER BIOLOGY & THERAPY, 2008, 7 (01)
[26]   EGF promotes HIF-1α expression in colorectal cancer cells and tumor metastasis by regulating phosphorylation of STAT3 [J].
Zhao, F. -L. ;
Qin, C. -F. .
EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES, 2019, 23 (03) :1055-1062
[27]   Translational suppression of HIF-1α by miconazole through the mTOR signaling pathway [J].
Park, Jee-Young ;
Jung, Hui-Jung ;
Seo, Incheol ;
Jha, Bijay Kumar ;
Suh, Seong-Il ;
Suh, Min-Ho ;
Baek, Won-Ki .
CELLULAR ONCOLOGY, 2014, 37 (04) :269-279
[28]   Anticancer Activity of Natural Flavonoids: Inhibition of HIF-1α Signaling Pathway [J].
Deng, Xiangping ;
Peng, Yijiao ;
Zhao, Jingduo ;
Lei, Xiaoyong ;
Zheng, Xing ;
Xie, Zhizhong ;
Tang, Guotao .
CURRENT ORGANIC CHEMISTRY, 2019, 23 (26) :2945-2959
[29]   Troxerutin regulates HIF-1α by activating JAK2/STAT3 signaling to inhibit oxidative stress, inflammation, and apoptosis of cardiomyocytes induced by H2O2 [J].
Li, Hui ;
Yang, Min ;
Lou, Danfei .
DRUG DEVELOPMENT RESEARCH, 2022, 83 (02) :552-563
[30]   Epilepsy Associates with Decreased HIF-1α/STAT5b Signaling in Glioblastoma [J].
Berendsen, Sharon ;
Spliet, Wim G. M. ;
Geurts, Marjolein ;
Van Hecke, Wim ;
Seute, Tatjana ;
Snijders, Tom J. ;
Bours, Vincent ;
Bell, Erica H. ;
Chakravarti, Arnab ;
Robe, Pierre A. .
CANCERS, 2019, 11 (01)
12345