Mechanism of Stat1 in the neuronal Ca2+ overload after intracerebral hemorrhage via the H3K27ac/Trpm7 axis.

Abstract

Intracerebral hemorrhage (ICH) is classified as a subtype of stroke and calcium (Ca2+) overload is a catalyst for ICH. This study explored the mechanisms of Stat1 (signal transducer and activator of transcription 1) in the neuronal Ca2+ overload after ICH. ICH mouse models and in vitro cell models were established. Stat1 and transient receptor potential melastatin 7 (Trpm7) were detected upregulated in ICH models. Afterward, the mice were infected with the lentivirus containing sh-Stat1, and HT22 cells were treated with si-Stat1 and the lentivirus containing pcDNA3.1-Trpm7. The neurological functional impairment, histopathological damage, and Nissl bodies in mice were all measured. HT22 cell viability and apoptosis were identified. The levels of Ca2+, Trpm7 mRNA, H3K27 acetylation (H3K27ac), CaMKII-α, and p-Stat1 protein in the tissues and cells were determined. We found that silencing Stat1 alleviated ICH damage and repressed the neuronal Ca2+ overload after ICH. H3K27ac enrichment in the Trpm7 promoter region was examined and we found that p-Stat1 accelerated Trpm7 transcription via promoting H3K27ac in the Trpm7 promoter region. Besides, Trpm7 overexpression increased Ca2+ overload and aggravated ICH. Overall, p-Stat1 promoted Trpm7 transcription and further aggravated the Ca2+ overload after ICH.NEW & NOTEWORTHY We found Stat1 promotes Trpm7 transcription by promoting H3K27 acetylation and thus promotes calcium overload of neurons after intracerebral hemorrhage.