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

页数：11

共 50 条

[31] Hyperactivation of IL-6/STAT3 pathway leaded to the poor prognosis of post-TACE HCCs by HIF-1α/SNAI1 axis-induced epithelial to mesenchymal transition [J].

Gai, Xiaohong ;

Zhou, Peng ;

Xu, Meng ;

Liu, Zhikui ;

Zheng, Xin ;

Liu, Qingguang .

JOURNAL OF CANCER, 2020, 11 (03) :570-582

[32] EGCG attenuated spinal cord injury by inhibiting ferroptosis via activation of HMOX1 expression and suppression of HIF-1 signaling pathway [J].

Yang, Han ;

Ye, Fei ;

Chen, Liuxu ;

Yang, Linyu ;

Kang, Jianping .

IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES, 2025, 28 (06) :799-807

[33] Discovery of P3971 an Orally Efficacious Novel Anticancer Agent Targeting HIF-1α and STAT3 Pathways [J].

Godse, Pallavi ;

Kumar, Pramod ;

Yewalkar, Nilambari ;

Deore, Vijaykumar ;

Lohar, Manoj ;

Mundada, Ramswaroop ;

Padgaonkar, Amol ;

Manohar, Sonal ;

Joshi, Asavari ;

Bhatia, Dimple ;

Desai, Nikesh ;

Damre, Anagha ;

Bhonde, Mandar ;

Joshi, Kalpana ;

Sharma, Rajiv ;

Kumar, Sanjay .

ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 2013, 13 (09) :1460-1466

[34] The role of lipids in promoting hair growth through HIF-1 signaling pathway [J].

Seo, Jieun ;

Matsumoto, Kotone ;

Nanmo, Ayaka ;

Tu, Shan ;

Jeong, Do-Won ;

Chun, Yang-Sook ;

Yan, Lei ;

Kageyama, Tatsuto ;

Fukuda, Junji .

SCIENTIFIC REPORTS, 2025, 15 (01) :4621

[35] HIF-1α Regulates Glucocorticoid-Induced Osteoporosis Through PDK1/AKT/mTOR Signaling Pathway [J].

Xu, Wen-Ning ;

Zheng, Huo-Liang ;

Yang, Run-Ze ;

Jiang, Lei-Sheng ;

Jiang, Sheng-Dan .

FRONTIERS IN ENDOCRINOLOGY, 2020, 10

[36] Hypobaric hypoxia exposure impairs colonic goblet cell subpopulation via the HIF-1α signaling pathway [J].

Zhang, Shaojie ;

Jiang, Xiufang ;

Zhang, Wangjingyi ;

Meng, Fansen ;

Gao, Jiayue ;

Cheng, Xiang ;

Hu, Yazhuo ;

Liu, Jing ;

Zhao, Tong ;

Zhu, Lingling ;

Wang, Gangshi .

AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2025, 328 (05) :G465-G478

[37] HIF-1α Induced by Hypoxia Promotes Peripheral Nerve Injury Recovery Through Regulating Ferroptosis in DRG Neuron [J].

An, Shuai ;

Shi, Jingfei ;

Huang, Jiang ;

Li, Zheng ;

Feng, Mingli ;

Cao, Guanglei .

MOLECULAR NEUROBIOLOGY, 2024, 61 (09) :6300-6311

[38] Vitexin alleviates interleukin-1β-induced inflammatory responses in chondrocytes from osteoarthritis patients: Involvement of HIF-1α pathway [J].

Yang, Hongpeng ;

Huang, Jian ;

Mao, Yanfang ;

Wang, Lin ;

Lie, Ruodong ;

Ha, Chengzhi .

SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 2019, 90 (02)

[39] Downregulation of Rab17 promotes cell proliferation and invasion in non-small cell lung cancer through STAT3/HIF-1α/VEGF signaling [J].

Wang, Mingliang ;

Wang, Wendong ;

Ding, Jingmin ;

Wang, Jiashun ;

Zhang, Jun .

THORACIC CANCER, 2020, 11 (02) :379-388

[40] Effects of IL-6R Expression on IL-6/STAT3/HIF-1α Signaling Pathway in a Mouse Model of Parkinson's Disease with Type 2 Diabetes Co-Morbidity [J].

Hu, Aiping ;

She, Yuqing ;

Wang, Yang ;

Cao, Xue ;

Li, Ran ;

Wang, Jing ;

Yu, Lizhi ;

Jiang, Haifeng ;

Zhao, Yang .

DISCOVERY MEDICINE, 2024, 36 (186) :1386-1397

← 1 2 3 4 5 →