Astrocytic AEG‐1 regulates expression of TREK‐1 under acute hypoxia

• Published in: Cell biochemistry and function 2020-03, Vol.38 (2), p.167-175
• Main Authors: Kim, Ajung, Jung, Hyun‐Gug, Kim, Seung‐Chan, Choi, Minji, Park, Jae‐Yong, Lee, Seok‐Geun, Hwang, Eun Mi
• Format: Article
• Language: English
• Subjects: AEG‐1; Animals; Apoptosis; astrocyte; Astrocytes; Astrocytes - cytology; Astrocytes - metabolism; Cell Hypoxia; Conductance; Electroporation; Gene expression; Glutamic Acid - metabolism; HEK293 Cells; Hif1α; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Infarction, Middle Cerebral Artery - metabolism; Male; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; mRNA; Neurons - metabolism; Potassium channels; Potassium Channels, Tandem Pore Domain - metabolism; Resistance; RNA, Messenger - metabolism; RNA-Binding Proteins - metabolism; TREK‐1
• ISSN: 0263-6484; 1099-0844
• DOI: 10.1002/cbf.3469

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.