抑制OGR1及G2A表現可藉由調控非IB4神經元鈣訊號減緩酸所誘導長期疼痛;Knockdown of both OGR1 and G2A relieves acid-induced pain by modulating calcium signals in IB4-negative neurons

NCUIR > college of Health Sciences and Technology > Graduate Institute of Life Science > Electronic Thesis & Dissertation > Item 987654321/80465

Please use this identifier to cite or link to this item: http://ir.lib.ncu.edu.tw/handle/987654321/80465

Title:	抑制OGR1及G2A表現可藉由調控非IB4神經元鈣訊號減緩酸所誘導長期疼痛;Knockdown of both OGR1 and G2A relieves acid-induced pain by modulating calcium signals in IB4-negative neurons
Authors:	李家維;Lee, Chia-Wei
Contributors:	生命科學系
Keywords:	疼痛;痛覺過敏感;長期疼痛;hyperalgesia;pain;OGR1;G2A;hyperalgesic priming
Date:	2019-08-26
Issue Date:	2019-09-03 14:33:43 (UTC+8)
Publisher:	國立中央大學
Abstract:	在各種病變和損傷中發現高局部濃度的氫離子，例如纖維肌痛，免疫疾病或關節炎，是慢性疼痛的一部分。組織酸中毒引發信號轉換（酸注射後2-4小時）從Gs-蛋白激酶A（PKA）到Gi-蛋白激酶Cε（PKCε），PKA-PKCε信號開關與痛覺過敏引發的發展相關。酸敏感G蛋白偶聯受體，包括OGR1，G2A，TDAG8和GPR4，可能是介導PKA-PKCε信號轉換的主要候選者。我們以前發現T細胞死亡相關基因8（TDAG8）介導酸中毒信號並與Gs蛋白偶聯以激活PKA途徑，引發痛覺過敏。 TDAG8-Gs-PKA途徑也參與痛覺過敏的引發。然而，PKA-PKCε信號轉換的潛在機制仍不清楚。在這項研究中，我們使用shRNA技術來探索從急性疼痛到慢性疼痛的轉變。在二次注射酸模型中（酸[pH5.0]注射兩次，間隔5天），給予G2A-和OGR1-shRNA質粒顯著抑制第一次痛覺過敏的延長期（4小時後）並縮短其持續時間。第二次痛覺過敏對應於Gi-PKCε信號傳導的作用時間。鑑於G2A和OGR1的異聚體介導Gi信號傳導，G2A和OGR1可通過調節Gi-PKCε信號傳導參與痛覺過敏引發的建立。;High local concentration of protons was found in kinds of lesions and injury, such as fibromyalgia, immune disease or arthritis, accounted for part of chronic pain. Tissue acidosis triggers a signal switch (2-4hr after acid injection) from Gs-protein kinase A (PKA) to Gi-protein kinase Cε (PKCε) and the PKA-to-PKCε signal switch is associated with development of hyperalgesic priming. Proton-sensing G-protein-coupled receptors including OGR1, G2A, TDAG8, and GPR4, could be major candidates to mediate the PKA-to-PKCε signal switch. We have previously found that T-cell death-associated gene 8 (TDAG8) mediates acidosis signals and couples to Gs protein to activate PKA pathway, initiating hyperalgesia. TDAG8-Gs-PKA pathway also participates in the establishment of hyperalgesic priming. However, the mechanism underlying the PKA-to-PKCε signal switch remains unclear. In this study, we used shRNA knockdown technique to explore the transition from acute to chronic pain. In the dual acid injection model (acid [pH5.0] injected twice, 5 days apart), administration of both G2A- and OGR1-shRNA plasmids significantly inhibited the prolonged phase (after 4hr) of the first hyperalgesia and shortened the duration of the second hyperalgesia, which corresponds to the action time of the Gi-PKCε signaling. Given that a heteromer of G2A and OGR1 mediates Gi-signaling, G2A and OGR1 may participate in the establishment of hyperalgesic priming through regulation of the Gi-PKCε signaling.
Appears in Collections:	[Graduate Institute of Life Science] Electronic Thesis & Dissertation

Files in This Item:

File	Description	Size	Format
index.html		0Kb	HTML	228	View/Open

社群 sharing

Loading...