Receptor tyrosine and MAP kinase are involved in effects of H2O2 on interstitial cells of Cajal in murine intestine

Hydrogen peroxide (H2O2) is involved in intestinal motility through changes of smooth muscle activity. However, there is no report as to the modulatory effects of H2O2 on interstitial cells of Cajal (ICC). We investigated the H2O2 effects and signal transductions to determine whether the intestinal...

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Main Authors:	Choi, Seok, Yeum, Cheol Ho, Kim, Young Dae, Park, Chan Guk, Kim, Man Yoo, Park, Jong-Seong, Jeong, Han-Seong, Kim, Byung Joo, So, Insuk, Kim, Ki Whan, Jun, Jae Yeoul
Format:	Online
Language:	English
Published:	Blackwell Publishing Ltd 2010
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837618/

id	pubmed-3837618
recordtype	oai_dc
spelling	pubmed-38376182015-04-24 Receptor tyrosine and MAP kinase are involved in effects of H2O2 on interstitial cells of Cajal in murine intestine Choi, Seok Yeum, Cheol Ho Kim, Young Dae Park, Chan Guk Kim, Man Yoo Park, Jong-Seong Jeong, Han-Seong Kim, Byung Joo So, Insuk Kim, Ki Whan Jun, Jae Yeoul Articles Hydrogen peroxide (H2O2) is involved in intestinal motility through changes of smooth muscle activity. However, there is no report as to the modulatory effects of H2O2 on interstitial cells of Cajal (ICC). We investigated the H2O2 effects and signal transductions to determine whether the intestinal motility can be modulated through ICC. We performed whole-cell patch clamp in cultured ICC from murine intestine and molecular analyses. H2O2 hyperpolarized the membrane and inhibited pacemaker currents. These effects were inhibited by glibenclamide, an inhibitor of ATP-sensitive K+ (KATP) channels. The free-radical scavenger catalase inhibited the H2O2-induced effects. MAFP and AACOCF3 (a cytosolic phospholipase A2 inhibitors) or SC-560 and NS-398 (a selective COX-1 and 2 inhibitor) or AH6809 (an EP2 receptor antagonist) inhibited the H2O2-induced effects. PD98059 (a mitogen activated/ERK-activating protein kinase inhibitor) inhibited the H2O2-induced effects, though SB-203580 (a p38 MAPK inhibitor) or a JNK inhibitor did not affect. H2O2-induced effects could not be inhibited by LY-294002 (an inhibitor of PI3-kinases), calphostin C (a protein kinase C inhibitor) or SQ-22536 (an adenylate cyclase inhibitor). Adenoviral infection analysis revealed H2O2 stimulated tyrosine kinase activity and AG 1478 (an antagonist of epidermal growth factor receptor tyrosine kinase) inhibited the H2O2-induced effects. These results suggest H2O2 can modulate ICC pacemaker activity and this occur by the activation of KATP channels through PGE2 production via receptor tyrosine kinase-dependent MAP kinase activation. Blackwell Publishing Ltd 2010 2008-07-10 /pmc/articles/PMC3837618/ /pubmed/20414970 http://dx.doi.org/10.1111/j.1582-4934.2008.00403.x Text en © 2008 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Choi, Seok Yeum, Cheol Ho Kim, Young Dae Park, Chan Guk Kim, Man Yoo Park, Jong-Seong Jeong, Han-Seong Kim, Byung Joo So, Insuk Kim, Ki Whan Jun, Jae Yeoul
spellingShingle	Choi, Seok Yeum, Cheol Ho Kim, Young Dae Park, Chan Guk Kim, Man Yoo Park, Jong-Seong Jeong, Han-Seong Kim, Byung Joo So, Insuk Kim, Ki Whan Jun, Jae Yeoul Receptor tyrosine and MAP kinase are involved in effects of H2O2 on interstitial cells of Cajal in murine intestine
author_facet	Choi, Seok Yeum, Cheol Ho Kim, Young Dae Park, Chan Guk Kim, Man Yoo Park, Jong-Seong Jeong, Han-Seong Kim, Byung Joo So, Insuk Kim, Ki Whan Jun, Jae Yeoul
author_sort	Choi, Seok
title	Receptor tyrosine and MAP kinase are involved in effects of H2O2 on interstitial cells of Cajal in murine intestine
title_short	Receptor tyrosine and MAP kinase are involved in effects of H2O2 on interstitial cells of Cajal in murine intestine
title_full	Receptor tyrosine and MAP kinase are involved in effects of H2O2 on interstitial cells of Cajal in murine intestine
title_fullStr	Receptor tyrosine and MAP kinase are involved in effects of H2O2 on interstitial cells of Cajal in murine intestine
title_full_unstemmed	Receptor tyrosine and MAP kinase are involved in effects of H2O2 on interstitial cells of Cajal in murine intestine
title_sort	receptor tyrosine and map kinase are involved in effects of h2o2 on interstitial cells of cajal in murine intestine
description	Hydrogen peroxide (H2O2) is involved in intestinal motility through changes of smooth muscle activity. However, there is no report as to the modulatory effects of H2O2 on interstitial cells of Cajal (ICC). We investigated the H2O2 effects and signal transductions to determine whether the intestinal motility can be modulated through ICC. We performed whole-cell patch clamp in cultured ICC from murine intestine and molecular analyses. H2O2 hyperpolarized the membrane and inhibited pacemaker currents. These effects were inhibited by glibenclamide, an inhibitor of ATP-sensitive K+ (KATP) channels. The free-radical scavenger catalase inhibited the H2O2-induced effects. MAFP and AACOCF3 (a cytosolic phospholipase A2 inhibitors) or SC-560 and NS-398 (a selective COX-1 and 2 inhibitor) or AH6809 (an EP2 receptor antagonist) inhibited the H2O2-induced effects. PD98059 (a mitogen activated/ERK-activating protein kinase inhibitor) inhibited the H2O2-induced effects, though SB-203580 (a p38 MAPK inhibitor) or a JNK inhibitor did not affect. H2O2-induced effects could not be inhibited by LY-294002 (an inhibitor of PI3-kinases), calphostin C (a protein kinase C inhibitor) or SQ-22536 (an adenylate cyclase inhibitor). Adenoviral infection analysis revealed H2O2 stimulated tyrosine kinase activity and AG 1478 (an antagonist of epidermal growth factor receptor tyrosine kinase) inhibited the H2O2-induced effects. These results suggest H2O2 can modulate ICC pacemaker activity and this occur by the activation of KATP channels through PGE2 production via receptor tyrosine kinase-dependent MAP kinase activation.
publisher	Blackwell Publishing Ltd
publishDate	2010
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837618/
_version_	1612030044712992768

Receptor tyrosine and MAP kinase are involved in effects of H2O2 on interstitial cells of Cajal in murine intestine

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