| First Author | Wang T | Year | 2020 |
| Journal | Stroke | Volume | 51 |
| Issue | 12 | Pages | 3690-3700 |
| PubMed ID | 33059544 | Mgi Jnum | J:302493 |
| Mgi Id | MGI:6508169 | Doi | 10.1161/STROKEAHA.120.031479 |
| Citation | Wang T, et al. (2020) GPR68 Is a Neuroprotective Proton Receptor in Brain Ischemia. Stroke 51(12):3690-3700 |
| abstractText | BACKGROUND AND PURPOSE: Brain acidosis is prevalent in stroke and other neurological diseases. Acidosis can have paradoxical injurious and protective effects. The purpose of this study is to determine whether a proton receptor exists in neurons to counteract acidosis-induced injury. METHODS: We analyzed the expression of proton-sensitive GPCRs (G protein-coupled receptors) in the brain, examined acidosis-induced signaling in vitro, and studied neuronal injury using in vitro and in vivo mouse models. RESULTS: GPR68, a proton-sensitive GPCR, was present in both mouse and human brain, and elicited neuroprotection in acidotic and ischemic conditions. GPR68 exhibited wide expression in brain neurons and mediated acidosis-induced PKC (protein kinase C) activation. PKC inhibition exacerbated pH 6-induced neuronal injury in a GPR68-dependent manner. Consistent with its neuroprotective function, GPR68 overexpression alleviated middle cerebral artery occlusion-induced brain injury. CONCLUSIONS: These data expand our knowledge on neuronal acid signaling to include a neuroprotective metabotropic dimension and offer GPR68 as a novel therapeutic target to alleviate neuronal injuries in ischemia and multiple other neurological diseases. |
