التفاصيل البيبلوغرافية
| العنوان: |
GPR68 Contributes to Persistent Acidosis-Induced Activation of AGC Kinases and Tyrosine Phosphorylation in Organotypic Hippocampal Slices |
| المؤلفون: |
Guokun Zhou, Xiang-ming Zha |
| المصدر: |
Frontiers in Neuroscience, Vol 15 (2021) |
| بيانات النشر: |
Frontiers Media S.A., 2021. |
| سنة النشر: |
2021 |
| المجموعة: |
LCC:Neurosciences. Biological psychiatry. Neuropsychiatry |
| مصطلحات موضوعية: |
neuronal injury, acid signaling, GPR68 (OGR1), phosphorylation, hippocampal slice, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571 |
| الوصف: |
Persistent acidosis occurs in ischemia and multiple neurological diseases. In previous studies, acidic stimulation leads to rapid increase in intracellular calcium in neurons. However, it remains largely unclear how a prolonged acidosis alters neuronal signaling. In our previous study, we found that GPR68-mediated PKC activities are protective against acidosis-induced injury in cortical slices. Here, we first asked whether the same principle holds true in organotypic hippocampal slices. Our data showed that 1-h pH 6 induced PKC phosphorylation in a GPR68-dependent manner. Go6983, a PKC inhibitor worsened acidosis-induced neuronal injury in wild type (WT) but had no effect in GPR68−/− slices. Next, to gain greater insights into acid signaling in brain tissue, we treated organotypic hippocampal slices with pH 6 for 1-h and performed a kinome profiling analysis by Western blot. Acidosis had little effect on cyclin-dependent kinase (CDK) or casein kinase 2 activity, two members of the CMGC family, or Ataxia telangiectasia mutated (ATM)/ATM and RAD3-related (ATR) activity, but reduced the phosphorylation of MAPK/CDK substrates. In contrast, acidosis induced the activation of CaMKIIα, PKA, and Akt. Besides these serine/threonine kinases, acidosis also induced tyrosine phosphorylation. Since GPR68 is widely expressed in brain neurons, we asked whether GPR68 contributes to acidosis-induced signaling. Deleting GPR68 had no effect on acidosis-induced CaMKII phosphorylation, attenuated that of phospho-Akt and phospho-PKA substrates, while abolishing acidosis-induced tyrosine phosphorylation. These data demonstrate that prolonged acidosis activates a network of signaling cascades, mediated by AGC kinases, CaMKII, and tyrosine kinases. GPR68 is the primary mediator for acidosis-induced activation of PKC and tyrosine phosphorylation, while both GPR68-dependent and -independent mechanisms contribute to the activation of PKA and Akt. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1662-453X |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fnins.2021.692217/full; https://doaj.org/toc/1662-453X |
| DOI: |
10.3389/fnins.2021.692217 |
| URL الوصول: |
https://doaj.org/article/f12fcd1fd9194486ba541541f3b47d20 |
| رقم الانضمام: |
edsdoj.f12fcd1fd9194486ba541541f3b47d20 |
| قاعدة البيانات: |
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