Knockdown of apoptosis signal-regulating kinase 1 affects ischaemia-induced astrocyte activation and glial scar formation

The European Journal of Neuroscience
So Yeong CheonGyung W Kim

Abstract

Reactive astrocytes play an essential role in determining the tissue response to ischaemia. Formation of a glial scar can block the neuronal outgrowth that is required for restoration of damaged tissue. Therefore, regulation of astrocyte activation is important; however, the mediator of this process has not been fully elucidated. Apoptosis signal-regulating kinase 1 (ASK1) is an early responder to oxidative stress, and plays a pivotal role in the intracellular signalling pathway of apoptosis, inflammation, and differentiation. To confirm whether ASK1 mediates astrocyte activation and leads to glial scar formation after cerebral ischaemia, we conducted in vivo and in vitro experiments. C57BL/6 mice were subjected to occlusion of the middle cerebral artery, and astrocyte cultures were exposed to oxygen-glucose deprivation. After silencing of ASK1 , astrocyte-associated genes were downregulated, as seen with the use of microarrays. The glial fibrillary acidic protein (GFAP) level was decreased, and correlated with the reduction in the ASK1 level. In astrocytes, reduction in the ASK1 level decreased the activity of the p38 pathway, and the levels of transcription factors for GFAP and GFAP transcripts after hypoxia. In the chronic p...Continue Reading

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Citations

Jan 9, 2019·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·So Yeong Cheon, Kyoung Joo Cho
Feb 7, 2019·Environmental Science and Pollution Research International·Mohamed A El-SakhawyYasmine H Ahmed
Aug 21, 2018·Current Drug Targets·Jahangir Alam, Lalit Sharma
Oct 1, 2017·Experimental and Therapeutic Medicine·Shuquan ZhangRui Gu
May 11, 2018·Oxidative Medicine and Cellular Longevity·So Yeong CheonBon-Nyeo Koo
Dec 13, 2019·Neuroscience Letters·Tianzun LiYongzhi Xia
Dec 8, 2021·Journal of Cellular and Molecular Medicine·Nehad F MazenAmal S El-Shal

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