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

Ajung Kim, Hyun Gug Jung, Seung Chan Kim, Minji Choi, Jae Yong Park, Seok Geun Lee, Eun Mi Hwang

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalCell Biochemistry and Function
DOIs
Publication statusAccepted/In press - 2019 Jan 1

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Keywords

  • AEG-1
  • astrocyte
  • Hif1α
  • hypoxia
  • TREK-1

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology

Cite this

Kim, A., Jung, H. G., Kim, S. C., Choi, M., Park, J. Y., Lee, S. G., & Hwang, E. M. (Accepted/In press). Astrocytic AEG-1 regulates expression of TREK-1 under acute hypoxia. Cell Biochemistry and Function. https://doi.org/10.1002/cbf.3469