Kim, Ajung Jung, Hyun-Gug Kim, Seung-Chan Choi, Minji Park, Jae-Yong Lee, Seok-Geun Hwang, Eun Mi 2024-01-19T18:03:07Z 2024-01-19T18:03:07Z 2021-09-04 2020-03 0263-6484 https://pubs.kist.re.kr/handle/201004/118936 TREK-1 (TWIK-related K+ channel), a member of the two-pore domain K+ (K2P) channel family, is highly expressed in astrocytes, where it plays a key role in glutamate release and passive conductance. In addition, TREK-1 is induced to protect neurons under pathological conditions such as hypoxia. However, the upstream regulation of TREK-1 remains poorly understood. In this study, we found that AEG-1 (astrocyte elevated gene-1) regulates the expression of astrocytic TREK-1 under hypoxic conditions. Upregulation of AEG-1 increased expression of TREK-1 in astrocytes, and knockdown of AEG-1 dramatically decreased the mRNA and protein levels of TREK-1, which were restored by expression of shRNA-insensitive AEG-1. In addition, expression of TREK-1 was not regulated in the absence of AEG-1, even when HIF1 alpha was present. Together, these results suggest that AEG-1 acts as a major upstream regulator of TREK-1 channels in astrocytes under hypoxia. Significance of the study Previous studies have reported that hypoxia increases the expression of astrocytic TREK-1 and that increased TREK-1 expression protects neuronal cells from apoptosis. However, its cellular mechanism is not clear. In this study we first showed that AEG-1 is a major mediator of hypoxic-regulated TREK-1 expression in normal astrocytes independently of HIF-1 alpha. English WILEY POTASSIUM CHANNELS ELEVATED GENE-1 NEUROPROTECTION ACTIVATION IDENTIFICATION CONDUCTANCE PATHWAYS ISCHEMIA CLONING Astrocytic AEG-1 regulates expression of TREK-1 under acute hypoxia Article 10.1002/cbf.3469 1 CELL BIOCHEMISTRY AND FUNCTION, v.38, no.2, pp.167 - 175 CELL BIOCHEMISTRY AND FUNCTION 38 2 167 175 scie scopus 000499058500001 2-s2.0-85075752308 Biochemistry & Molecular Biology Cell Biology Biochemistry & Molecular Biology Cell Biology Article POTASSIUM CHANNELS ELEVATED GENE-1 NEUROPROTECTION ACTIVATION IDENTIFICATION CONDUCTANCE PATHWAYS ISCHEMIA CLONING AEG-1 astrocyte Hif1 alpha hypoxia TREK-1