当前位置： SCI文献检索 > BRITISH JOURNAL OF PHARMACOLOGY期刊下所有文献 > The effect of tyrosine nitration of L-type Ca2+ channels on excitation-transcription coupling in colonic inflammation.

The effect of tyrosine nitration of L-type Ca2+ channels on excitation-transcription coupling in colonic inflammation.

Abstract：

BACKGROUND AND PURPOSE:Excitation-transcriptional coupling involves communication between plasma membrane ion channels and gene expression in the nucleus. Calcium influx through L-type Ca(2+) channels induces phosphorylation of the transcription factor, cyclic-AMP response element binding protein (CREB) and downstream activation of the cyclic-AMP response element (CRE) promoter regions. Tyrosine nitration of Ca(2+) channels attenuates interactions with c-Src kinase, decreasing Ca(2+) channel currents and smooth muscle contraction during colonic inflammation. In this study we examined the effect of tyrosine nitration and colonic inflammation on Ca(2+) channel mediated phosphorylation of CREB and CRE activation. EXPERIMENTAL APPROACH:CREB and phospho-CREB were detected by Western blots and CRE activation measured by dual luciferase assay. Chinese hamster ovary (CHO) cells were transfected with hCa(v)1.2b and hCa(v)1.2b c-terminal mutants. Colonic inflammation was induced by intracolonic instillation of 2,4,6 trinitrobenzene sulphonic acid in mouse colon. KEY RESULTS:In hCa(v)1.2b transfected CHO cells and in native colonic smooth muscle, depolarization with 80 mM KCl induced CREB phosphorylation (pCREB). Treatment with peroxynitrite inhibited KCl-induced pCREB. Following experimental colitis, KCl-induced CREB phosphorylation was abolished in smooth muscle, concomitant with tyrosine nitration of Ca(2+) channels. Depolarization increased CRE activation in hCa(v)1.2b CHO cells by 2.35 fold which was blocked by nifedipine and by protein nitration of Ca(2+) channels with peroxynitrite. The Src-kinase inhibitor, PP2, blocked depolarization-induced CRE activation. Mutation of the C-terminus tyrosine residue, Y2134F, but not Y1861F, blocked CRE activation. CONCLUSIONS AND IMPLICATIONS:Post-translational modification of Ca(2+) channels due to tyrosine nitration modified excitation-transcriptional coupling in colonic inflammation.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Kang M,Ross GR,Akbarali HI

doi

10.1111/j.1476-5381.2009.00599.x

subject

Has Abstract

pub_date

2010-03-01 00:00:00

pages

1226-35

issue

eissn

0007-1188

issn

1476-5381

pii

BPH599

journal_volume

159

pub_type

杂志文章

在线工具

The effect of tyrosine nitration of L-type Ca2+ channels on excitation-transcription coupling in colonic inflammation.