HDAC9 promotes brain ischemic injury by provoking IκBα/NF-κB and MAPKs signaling pathways

Biochemical and Biophysical Research Communications
Shan LuXiao-Di Fan

Abstract

Ischemic stroke is an acute cerebrovascular disease due to poor blood flow to the brain. Nevertheless, there is still no effective therapy for it and the pathology contributing to ischemic stroke is not fully understood. Histone Deacetylase 9 (HDAC9) is a class IIa chromatin-modifying enzyme. HDAC9 gene region is a leading risk locus for large artery atherosclerotic stroke. However, the mechanisms linking HDAC9 to ischemic remain elusive. In the study, we attempted to explore HDAC9-associated inflammatory response using the wild type (WT) and HDAC9-knockout (KO) mice with brain ischemic injury. The results indicated that WT mice with ischemia brain exhibited higher expression levels of HDAC9. HDAC9 depletion resulted in a decreased infarct volume and an improved neurological function in mice after ischemic reperfusion (I/R) injury. I/R injury markedly enhanced GFAP and Iba-1 expressions in cortex and HDAC9 knockout significantly reversed this up-regulation. Loss of HDAC9 inhibited the release of inducible NO-synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and IL-18 in cortex, hippocampus and hypothalamus of mice with I/R injury, which occurred at the transcription levels...Continue Reading

Citations

Sep 11, 2019·Stroke; a Journal of Cerebral Circulation·Matthias PrestelMartin Dichgans
May 8, 2020·International Journal of Molecular Sciences·Duk-Hwa KwonHyun Kook
Nov 24, 2020·Journal of Korean Neurosurgical Society·Xitong YangGuangming Wang
Dec 3, 2020·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Zhiqiang GaoYunxia Wu
Jun 20, 2021·Journal of Cellular and Molecular Medicine·Yanqin LiuHai-Yan Lin
Dec 23, 2021·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Xi KuangQifu Li

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