Premium
Astrocytic AEG‐1 regulates expression of TREK‐1 under acute hypoxia
Author(s) -
Kim Ajung,
Jung HyunGug,
Kim SeungChan,
Choi Minji,
Park JaeYong,
Lee SeokGeun,
Hwang Eun Mi
Publication year - 2020
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.3469
Subject(s) - astrocyte , gene knockdown , downregulation and upregulation , hypoxia (environmental) , microbiology and biotechnology , small hairpin rna , biology , glutamate receptor , apoptosis , chemistry , neuroscience , gene , biochemistry , central nervous system , receptor , oxygen , organic chemistry
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 HIF1α 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‐1α.