Astrocytic AEG-1 regulates expression of TREK-1 under acute hypoxia.
Cell Biochem Funct
; 38(2): 167-175, 2020 Mar.
Article
em En
| MEDLINE
| ID: mdl-31782179
ABSTRACT
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.
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MEDLINE
Assunto principal:
Hipóxia Celular
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Astrócitos
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Proteínas de Ligação a RNA
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Canais de Potássio de Domínios Poros em Tandem
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Subunidade alfa do Fator 1 Induzível por Hipóxia
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Proteínas de Membrana
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article