Adenosine Receptor A1-A2a Heteromers Regulate EAAT2 Expression and Glutamate Uptake via YY1-Induced Repression of PPARγ Transcription
Joint Authors
Hou, Xianhua
Li, Yuan
Huang, Yuanyuan
Zhao, Huan
Gui, Li
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-03-06
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Adenosine receptors A1 (A1AR) and A2a (A2aAR) play an important role in regulating glutamate uptake to avoid glutamate accumulation that causes excitotoxicity in the brain; however, the precise mechanism of the effects of A1AR and A2aAR is unclear.
Herein, we report that expression of the A1AR protein in the astrocyte membrane and the level of intracellular glutamate were decreased, while expression of the A2aR protein was elevated in cells exposed to oxygen-glucose deprivation (OGD) conditions.
Coimmunoprecipitation (Co-IP) experiments showed that A1AR interacts with A2aAR under OGD conditions.
The activation of A1AR and inactivation of A2aAR by 2-chloro-N6-cyclopentyladenosine (CCPA) and SCH58251, respectively, partly reversed OGD-mediated glutamate uptake dysfunction, elevated EAAT2, and PPARγ protein levels, and suppressed the expression of Ying Yang 1 (YY1).
Both the silencing of YY1 and the activation of PPARγ upregulated EAAT2 expression.
Moreover, YY1 silencing elevated the PPARγ level under both normal and OGD conditions.
Histone deacetylase (HDAC)1 was found to interact with YY1, and HDAC1 silencing improved PPARγ promoter activity.
Taken together, our findings suggest that A1AR-A2aAR heteromers regulate EAAT2 expression and glutamate uptake through the YY1-mediated recruitment of HDAC1 to the PPARγ promoter region.
American Psychological Association (APA)
Hou, Xianhua& Li, Yuan& Huang, Yuanyuan& Zhao, Huan& Gui, Li. 2020. Adenosine Receptor A1-A2a Heteromers Regulate EAAT2 Expression and Glutamate Uptake via YY1-Induced Repression of PPARγ Transcription. PPAR Research،Vol. 2020, no. 2020, pp.1-11.
https://search.emarefa.net/detail/BIM-1206591
Modern Language Association (MLA)
Hou, Xianhua…[et al.]. Adenosine Receptor A1-A2a Heteromers Regulate EAAT2 Expression and Glutamate Uptake via YY1-Induced Repression of PPARγ Transcription. PPAR Research No. 2020 (2020), pp.1-11.
https://search.emarefa.net/detail/BIM-1206591
American Medical Association (AMA)
Hou, Xianhua& Li, Yuan& Huang, Yuanyuan& Zhao, Huan& Gui, Li. Adenosine Receptor A1-A2a Heteromers Regulate EAAT2 Expression and Glutamate Uptake via YY1-Induced Repression of PPARγ Transcription. PPAR Research. 2020. Vol. 2020, no. 2020, pp.1-11.
https://search.emarefa.net/detail/BIM-1206591
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1206591