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Activation of adenosine A2a receptor accelerates and A2a receptor antagonist reduces intermittent hypoxia induced PC12 cell injury via PKC-KATP pathway
- Source :
- Brain research bulletin. 150
- Publication Year :
- 2019
-
Abstract
- Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with multiple system diseases. Neurocognitive dysfunction resulting from central nervous system complications has been reported, especially in children with OSAHS. Chronic intermittent hypoxia is accepted to be the major pathophysiological mechanism of OSAHS. Adenosine plays an important role in cellular function via interactions with its receptors. A2a receptor has been recognized as a factor involved in neuroprotection. However, the role of adenosine A2a receptor in intermittent hypoxia induced cellular injury is not completely understood. In this study, we aim to investigate the underlying mechanisms of A2a receptor mediated cellular damage caused by intermittent hypoxia in PC12 cells. We found that activated A2a receptor by CGS21680 decreased cellular viability, increased PKC as well as ATP-sensitive potassium channel (KATP) subunits expression Kir6.2 and SUR1. Inhibition of A2a receptor by SCH58261 increased cellular viability, suppressed PKC and SUR1 expression level, ultimately showing a protective role in PC12 cells. Moreover, we observed that CHE, which is an antagonist of PKC, downregulated Kir6.2 and SUR1 expression and increased cellular viability. Additionally, we found that A2a receptor activation induced cell injury was associated with increased Cleaved-Caspase 3 expression, which can be decreased by inhibition of A2a receptor or PKC. In conclusion, our findings indicate that A2a receptor induced KATP expression by PKC activation and plays a role in accelerating PC12 cells injury induced by intermittent hypoxia exposure via A2a-PKC-KATP signal pathway mediated apoptosis.
- Subjects :
- 0301 basic medicine
endocrine system
Adenosine
Potassium Channels
Adenosine A2 Receptor Agonists
Receptor, Adenosine A2A
medicine.drug_class
Adenosine A2A receptor
Sulfonylurea Receptors
Neuroprotection
PC12 Cells
03 medical and health sciences
Random Allocation
0302 clinical medicine
Adenosine Triphosphate
KATP Channels
Phenethylamines
medicine
Animals
Receptor
Protein kinase C
Protein Kinase C
Chemistry
General Neuroscience
Intermittent hypoxia
Kir6.2
Triazoles
Receptor antagonist
Cell Hypoxia
Cell biology
Adenosine A2 Receptor Antagonists
Rats
030104 developmental biology
Pyrimidines
030217 neurology & neurosurgery
medicine.drug
Signal Transduction
Subjects
Details
- ISSN :
- 18732747
- Volume :
- 150
- Database :
- OpenAIRE
- Journal :
- Brain research bulletin
- Accession number :
- edsair.doi.dedup.....4935e06894f4758aa866e0bd092fd036