p122 protein enhances intracellular calcium increase to acetylcholine: its possible role in the pathogenesis of coronary spastic angina

Arteriosclerosis, Thrombosis, and Vascular Biology
Reiichi MurakamiKen Okumura

Abstract

Phospholipase C-δ1 activity is enhanced in patients with coronary artery spasm, and a p122 protein was recently cloned to potentiate phospholipase C-δ1 activity. To investigate the role of p122 in enhanced vasomotility, we examined p122 expression in the cultured skin fibroblasts obtained from patients with and without coronary spasm, intracellular Ca(2+) concentration ([Ca(2+)]i) [corrected] at baseline and after stimulation with acetylcholine in the cells transfected with p122, and promoter in genomic DNA. [corrected] p122 protein and gene expression levels in patients with coronary spasm (n=11) were enhanced compared with levels in control subjects (n=9) (P<0.01 for both). [Ca(2+)](i) at baseline and the peak increase in [Ca(2+)](i) in response to acetylcholine were both 2 times higher in cells transfected with p122 than in those without p122. Conversely, knockdown of p122 resulted in diminished [Ca(2+)](i) response. In the p122 promoter analysis, the -228G/A and -1466C/T variants revealed the increase in luciferase activity. Although the -1466C/T variant was similar between 144 patients with coronary spasm and 148 controls, the -228G/A variant was more frequent in male patients than in male controls (P<0.05). The p122 prote...Continue Reading

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Citations

Sep 11, 2019·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Guochang ZhangGuanzheng Yang
Dec 2, 2015·PloS One·Takahiko KinjoKen Okumura
Mar 8, 2011·Circulation Journal : Official Journal of the Japanese Circulation Society·Tomohiro Osanai, Ken Okumura

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