Work

MAZ regulates ferroptosis, apoptosis and differentiation of oligodendrocyte precursor cells

Year: 2024

Type: article

Abstract: • MAZ is downregulated in the corpus callosum of demyelinating mice. • MAZ inhibits ferroptosis and apoptosis of oligodendrocyte precursor cells (OPCs). • MAZ promotes differentiation of OPCs. • MAZ binds to the promoter of SOX2 and activated its transcription. • MAZ/SOX2 axis promotes OPC survival/differentiation, thus relieving demyelination. Oligodendrocyte precursor cells (OPCs) respond rapidly to demyelination injury. However, the rescuing effects may be hindered by cell death of OPCs, leading to incomplete remyelination. This study aimed to explore the expression of MYC-associated zinc finger protein (MAZ) in demyelinated mice and the effects of MAZ on cell death form and differentiation of OPCs. Mice received demyelinating agent (cuprizone, CZ) for 5 weeks. Histological staining demonstrated that CZ feeding triggered demyelination in the corpus callosum (CC). Detection of iron content and ferroptosis markers indicated that ferroptosis was inducted in the CC of CZ-treated mice. Notably, we found CZ feeding resulted in a reduction of MAZ expression within the CC. Using CCK-8 assay, detection of iron content, MDA level, GSH level, and ferroptosis markers, lipid ROS detection, and immunofluorescence staining for 4-HNE, we found that knockdown of MAZ facilitated OPC ferroptosis. We also evaluated the susceptibility of MAZ-overexpressing OPCs to ferroptosis inducer, erastin, and demonstrated that MAZ-overexpressing OPCs were resistant to erastin-induced ferroptosis. TUNEL staining and western blot analysis indicated that MAZ knockdown promoted apoptosis of OPCs by inhibiting PI3K/Akt activation. Immunofluorescence staining of MBP indicated that knockdown of MAZ inhibited OPC differentiation. Moreover, we elucidate the mechanism responsible for MAZ’s protective effects on OPC death and differentiation, which may be achieved through transcriptional activation of SOX2. Our findings introduced MAZ as a beneficial modulator of OPC survival and differentiation, and it could serve as a potential therapeutic target for demyelination diseases.

Source: Brain Research

DOI: 10.1016/j.brainres.2024.149349

Authors: Fangkun Jing, Quancai Wang, Yangxi Xu, Jingyu Dong, Haitao Huang, Yanfeng Li

Institution: China Medical University

Language: English

Topic: Multiple Sclerosis Research Studies

Subfield: Pathology and Forensic Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,110