Silencing ATF3 mediates mitochondrial homeostasis and improves ischemic stroke through regulating the MAPK signaling pathway
Year: 2025
Type: article
Abstract: Mitochondrial homeostasis is crucial for preventing and treatment of ischemic stroke. This study aimed to investigate the role of activating transcription factor 3 (ATF3) in ischemic stroke and mitochondrial homeostasis. ATF3 was silenced in oxygen glucose deprivation/reperfusion (OGD/R)-treated HT22 cells to evaluate its effects on cell apoptosis and mitochondrial function. The effects of silencing ATF3 on neurological injury, infarction, adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (NAD+), mitofusin 1 (MFN1) and MFN2 were evaluated in stroke rats. Transcriptome sequencing and differential expression analysis were conducted to identify differential expressed genes (DEGs) associated with silencing ATF3, followed by functional enrichment analysis. The mitogen activated protein kinase (MAPK) agonist, anisomycin, was used to investigate the regulation of ATF3 in ischemic stroke and mitochondrial homeostasis via the MAPK pathway. Silencing ATF3 increased cell viability and inhibited apoptosis of OGD/R-induced cells. In stroke rats, silencing ATF3 reduced brain water content, decreased neurological injury and alleviated cerebral infarction. Notably, silencing ATF3 significantly inhibited the production of reactive oxygen species (ROS), increased the concentrations of ATP and NAD+, and upregulated the expression of MFN1 and MFN2. Next, 4,517 DGEs associated with silencing ATF3 were mainly enriched in MAPK signaling pathway. Silencing ATF3 downregulated the expression of phosphorylation-extracellular signal-regulated kinase (p-ERK)/ERK in OGD/R cells. Anisomycin notably reversed the effect of silencing ATF3 on ischemic stroke and mitochondrial homeostasis. Silencing ATF3 attenuates ischemic stroke and improves mitochondrial homeostasis via the MAPK signaling pathway, which shares a novel direction for maintaining mitochondrial homeostasis in ischemic stroke.
Authors: Haifengqing Li, Fan Zhang, Cong Zhang, Min Zhou, Qing Liu, Guoyong Zeng
Institution: Nanchang University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W4411500930