GPR68 Is a Neuroprotective Proton Receptor in Brain Ischemia

Date
2020-12
Language
American English
Embargo Lift Date
Committee Members
Degree
Degree Year
Department
Grantor
Journal Title
Journal ISSN
Volume Title
Found At
Lippincott, Williams & Wilkins
Abstract

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.

Description
item.page.description.tableofcontents
item.page.relation.haspart
Cite As
Wang, T., Zhou, G., He, M., Xu, Y., Rusyniak, W. G., Xu, Y., Ji, Y., Simon, R. P., Xiong, Z.-G., & Zha, X. (2020). GPR68 Is a Neuroprotective Proton Receptor in Brain Ischemia. Stroke, 51(12), 3690–3700. https://doi.org/10.1161/STROKEAHA.120.031479
ISSN
0039-2499, 1524-4628
Publisher
Series/Report
Sponsorship
Major
Extent
Identifier
Relation
Journal
Stroke
Source
Publisher
Alternative Title
Type
Article
Number
Volume
Conference Dates
Conference Host
Conference Location
Conference Name
Conference Panel
Conference Secretariat Location
Version
Final published version
Full Text Available at
This item is under embargo {{howLong}}