ALKBH5-mediated N6-methyladenosine modification of HO-1 mRNA regulates ferroptosis in cobalt-induced neurodegenerative damage

被引：3

作者：

Su, Qianqian ^{[1
]}

Wu, Lingyan ^{[1
]}

Zheng, Chunyan ^{[2
]}

Ji, Xianqi ^{[1
]}

Lin, Xinpei ^{[1
]}

Zhang, Yu ^{[1
]}

Zheng, Fuli ^{[1
]}

Guo, Zhenkun ^{[1
]}

Shao, Wenya ^{[1
]}

Hu, Hong ^{[1
]}

Zhou, Jinfu ^{[1
,2
]}

Jiang, Yu ^{[1
]}

Tang, Ying ^{[3
]}

Wu, Siying ^{[4
]}

Aschner, Michael ^{[5
]}

Li, Huangyuan ^{[1
]}

Yu, Guangxia ^{[1
]}

机构：

[1] Fujian Med Univ, Sch Publ Hlth, Dept Prevent Med, Key Lab Environm & Hlth, Fuzhou 350122, Peoples R China

[2] Fujian Med Univ, Fujian Matern & Child Hlth Hosp, Coll Clin Med Obstet & Gynecol & Pediat, Fuzhou 350001, Fujian, Peoples R China

[3] Fujian Ctr Prevent & Control Occupat Dis & Chem Po, Fuzhou 350125, Peoples R China

[4] Fujian Med Univ, Sch Publ Hlth, Dept Epidemiol & Hlth Stat, Fuzhou 350122, Peoples R China

[5] Albert Einstein Coll Med, Dept Mol Pharmacol, 1300 Morris Pk Ave, Bronx, NY 10461 USA

来源：

ENVIRONMENT INTERNATIONAL | 2024年 / 190卷

基金：

中国国家自然科学基金; 国家自然科学基金国际合作与交流项目;

关键词：

Cobalt; Ferroptosis; Epigenetic hazard; N6-methyladenosine demethylase; Neurodegenerative damage; OXIDATIVE STRESS; HEALTH; FLOWS; IRON; INHIBITION; EVOLUTION; APOPTOSIS; AUTOPHAGY; INSIGHTS; DISEASES;

D O I：

10.1016/j.envint.2024.108897

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

The utilization of Cobalt (Co) has surged due to it is critical role in renewable energy technologies and other high-tech applications. Concurrently, the potential health risks associated with Co exposure have raised concerns. Previous studies, including our own, have shown that Co can impair learn and memory functions as an epigenetic hazard, even at low concentrations. In this study, we explore the mechanisms of Co-induced ferroptosis in neurodegenerative damage both in vivo and in vitro, focusing on the epigenetic regulation by N6methyladenosine (m6A) demethylase alkB homolog 5 (ALKBH5). We identify heme oxygenase-1 (HO-1) as a direct target gene of ALKBH5, playing a crucial role in mitigating Co-induced ferroptosis. ALKBH5 deficiency affects the post-transcriptional regulation of HO-1 through m6A modification, which in turn influences mRNA's stability, intracellular distribution, and alternative splicing, thereby enhancing susceptibility to Co-induced ferroptosis. Additionally, we discuss the potential involvement of heterogeneous nuclear ribonucleoprotein M (hnRNPM) in regulating alternative splicing of HO-1 mRNA, potentially mediated by m6A modifications. This study provides new epigenetic insights into the post-transcriptional regulatory mechanisms involved in Coinduced ferroptosis and highlights the broader implications of environmental hazards in neurodegenerative damage.

引用

页数：19