Abstract
Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with the neurocognitive deficits as a result of the neuronal cell injury. Previous studies have shown that adenosine A1 receptor (ADORA1) played an important role against hypoxia exposure, such as controlling the metabolic recovery in rat hippocampal slices and increasing the resistance in the combined effects of hypoxia and hypercapnia. However, little is known about whether ADORA1 takes part in the course of neuronal cell injury after intermittent hypoxia exposure which was the main pathological characteristic of OSAHS. The present study is performed to explore the underlying mechanism of neuronal cell injury which was induced by intermittent hypoxia exposure in PC12 cells. In our research, we find that the stimulation of the ADORA1 by CCPA accelerated the injury of PC12 cells as well as upregulated the expression of PKC, inwardly rectifying potassium channel 6.2(Kir6.2) and sulfonylurea receptor 1(SUR1) while inhibition of the ADORA1 by DPCPX alleviated the injury of PC12 cells as well as downregulated the expression of PKC, Kir6.2, and SUR1. Moreover, inhibition of the PKC by CHE, also mitigated the injury of PC12 cells, suppressed the Kir6.2 and SUR1 expressions induced by PKC. Taken together, our findings indicate that ADORA1 accelerated PC12 cells injury after intermittent hypoxia exposure via ADORA1/PKC/KATP signaling pathway.
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Abbreviations
- ADORA1:
-
Adenosine A1 receptor
- PKC:
-
Protein kinase C
- KATP :
-
ATP-sensitive potassium channel
- OSAHS:
-
Obstructive sleep apnea hypopnea syndrome
- CCPA:
-
2-Chloro-N6-cyclopentyladenosine
- DPCPX:
-
8-Cyclopentyl-1, 3-dipropylxanthine
- CHE:
-
Chelerythrine chloride
- Kir:
-
Inwardly rectifying potassium channel
- SUR:
-
Sulfonylurea receptor
- IH:
-
Intermittent hypoxia
- SH:
-
Sustained hypoxia
- AC:
-
Air control
- CCK:
-
Cell Counting Kit
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Acknowledgements
This work was supported by Zhejiang Provincial Natural Science Foundation Grant (LY17H010004), Scientific Research Foundation of Health Bureau of Zhejiang Province (2018ZD010), Wenzhou City Science and Technology Bureau Grant (Y20170133), National Science-technology Support Program (2015BAI12B09), and Project of Key Innovative Disciplines of Children Sleep Medicine of Zhejiang.
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Mei, HF., Poonit, N., Zhang, YC. et al. Activating adenosine A1 receptor accelerates PC12 cell injury via ADORA1/PKC/KATP pathway after intermittent hypoxia exposure. Mol Cell Biochem 446, 161–170 (2018). https://doi.org/10.1007/s11010-018-3283-2
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DOI: https://doi.org/10.1007/s11010-018-3283-2