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

Seok Choi, Cheol Ho Yeum, Young Dae Kim, Chan Guk Park, Man Yoo Kim, Jong Seong Park, Han Seong Jeong, Byung Joo Kim, Insuk So, Ki Whan Kim, Jae Yeoul Jun

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Abstract

Hydrogen peroxide (H 2 O 2 ) is involved in intestinal motility through changes of smooth muscle activity. However, there is no report as to the modulatory effects of H 2 O 2 on interstitial cells of Cajal (ICC). We investigated the H 2 O 2 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. H 2 O 2 hyperpolarized the membrane and inhibited pacemaker currents. These effects were inhibited by glibenclamide, an inhibitor of ATP-sensitive K + (K ATP ) channels. The free-radical scavenger catalase inhibited the H 2 O 2 -induced effects. MAFP and AACOCF 3 (a cytosolic phospholipase A 2 inhibitors) or SC-560 and NS-398 (a selective COX-1 and 2 inhibitor) or AH6809 (an EP 2 receptor antagonist) inhibited the H 2 O 2 -induced effects. PD98059 (a mitogen activated/ERK-activating protein kinase inhibitor) inhibited the H 2 O 2 -induced effects, though SB-203580 (a p38 MAPK inhibitor) or a JNK inhibitor did not affect. H 2 O 2 -induced effects could not be inhibited by LY-294002 (an inhibitor of PI 3 -kinases), calphostin C (a protein kinase C inhibitor) or SQ-22536 (an adenylate cyclase inhibitor). Adenoviral infection analysis revealed H 2 O 2 stimulated tyrosine kinase activity and AG 1478 (an antagonist of epidermal growth factor receptor tyrosine kinase) inhibited the H 2 O 2 -induced effects. These results suggest H 2 O 2 can modulate ICC pacemaker activity and this occur by the activation of K ATP channels through PGE 2 production via receptor tyrosine kinase-dependent MAP kinase activation.

Original languageEnglish
Pages (from-to)257-266
Number of pages10
JournalJournal of Cellular and Molecular Medicine
Volume14
Issue number1-2
DOIs
StatePublished - 1 Jan 2010

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Interstitial Cells of Cajal
Receptor Protein-Tyrosine Kinases
Intestines
Gastrointestinal Motility
Adenosine Triphosphate
Protein Kinase Inhibitors
Protein-Tyrosine Kinases
TYK2 Kinase
Free Radical Scavengers
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Protein C Inhibitor
Glyburide
Phospholipases A
Cyclooxygenase 2 Inhibitors
Mitogen-Activated Protein Kinase Kinases
p38 Mitogen-Activated Protein Kinases
Prostaglandins E
Phosphatidylinositol 3-Kinases
Mitogens
Epidermal Growth Factor Receptor

Keywords

  • Cyclooxygenase
  • Hydrogen peroxide
  • Interstitial cells of Cajal
  • MAP kinase
  • Pacemaker currents
  • Receptor tyrosine kinase

Cite this

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. In: Journal of Cellular and Molecular Medicine. 2010 ; Vol. 14, No. 1-2. pp. 257-266.
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abstract = "Hydrogen peroxide (H 2 O 2 ) is involved in intestinal motility through changes of smooth muscle activity. However, there is no report as to the modulatory effects of H 2 O 2 on interstitial cells of Cajal (ICC). We investigated the H 2 O 2 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. H 2 O 2 hyperpolarized the membrane and inhibited pacemaker currents. These effects were inhibited by glibenclamide, an inhibitor of ATP-sensitive K + (K ATP ) channels. The free-radical scavenger catalase inhibited the H 2 O 2 -induced effects. MAFP and AACOCF 3 (a cytosolic phospholipase A 2 inhibitors) or SC-560 and NS-398 (a selective COX-1 and 2 inhibitor) or AH6809 (an EP 2 receptor antagonist) inhibited the H 2 O 2 -induced effects. PD98059 (a mitogen activated/ERK-activating protein kinase inhibitor) inhibited the H 2 O 2 -induced effects, though SB-203580 (a p38 MAPK inhibitor) or a JNK inhibitor did not affect. H 2 O 2 -induced effects could not be inhibited by LY-294002 (an inhibitor of PI 3 -kinases), calphostin C (a protein kinase C inhibitor) or SQ-22536 (an adenylate cyclase inhibitor). Adenoviral infection analysis revealed H 2 O 2 stimulated tyrosine kinase activity and AG 1478 (an antagonist of epidermal growth factor receptor tyrosine kinase) inhibited the H 2 O 2 -induced effects. These results suggest H 2 O 2 can modulate ICC pacemaker activity and this occur by the activation of K ATP channels through PGE 2 production via receptor tyrosine kinase-dependent MAP kinase activation.",
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author = "Seok Choi and Yeum, {Cheol Ho} and Kim, {Young Dae} and Park, {Chan Guk} and Kim, {Man Yoo} and Park, {Jong Seong} and Jeong, {Han Seong} and Kim, {Byung Joo} and Insuk So and Kim, {Ki Whan} and Jun, {Jae Yeoul}",
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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.

In: Journal of Cellular and Molecular Medicine, Vol. 14, No. 1-2, 01.01.2010, p. 257-266.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Receptor tyrosine and MAP kinase are involved in effects of H2O2 on interstitial cells of Cajal in murine intestine

AU - Choi, Seok

AU - Yeum, Cheol Ho

AU - Kim, Young Dae

AU - Park, Chan Guk

AU - Kim, Man Yoo

AU - Park, Jong Seong

AU - Jeong, Han Seong

AU - Kim, Byung Joo

AU - So, Insuk

AU - Kim, Ki Whan

AU - Jun, Jae Yeoul

PY - 2010/1/1

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N2 - Hydrogen peroxide (H 2 O 2 ) is involved in intestinal motility through changes of smooth muscle activity. However, there is no report as to the modulatory effects of H 2 O 2 on interstitial cells of Cajal (ICC). We investigated the H 2 O 2 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. H 2 O 2 hyperpolarized the membrane and inhibited pacemaker currents. These effects were inhibited by glibenclamide, an inhibitor of ATP-sensitive K + (K ATP ) channels. The free-radical scavenger catalase inhibited the H 2 O 2 -induced effects. MAFP and AACOCF 3 (a cytosolic phospholipase A 2 inhibitors) or SC-560 and NS-398 (a selective COX-1 and 2 inhibitor) or AH6809 (an EP 2 receptor antagonist) inhibited the H 2 O 2 -induced effects. PD98059 (a mitogen activated/ERK-activating protein kinase inhibitor) inhibited the H 2 O 2 -induced effects, though SB-203580 (a p38 MAPK inhibitor) or a JNK inhibitor did not affect. H 2 O 2 -induced effects could not be inhibited by LY-294002 (an inhibitor of PI 3 -kinases), calphostin C (a protein kinase C inhibitor) or SQ-22536 (an adenylate cyclase inhibitor). Adenoviral infection analysis revealed H 2 O 2 stimulated tyrosine kinase activity and AG 1478 (an antagonist of epidermal growth factor receptor tyrosine kinase) inhibited the H 2 O 2 -induced effects. These results suggest H 2 O 2 can modulate ICC pacemaker activity and this occur by the activation of K ATP channels through PGE 2 production via receptor tyrosine kinase-dependent MAP kinase activation.

AB - Hydrogen peroxide (H 2 O 2 ) is involved in intestinal motility through changes of smooth muscle activity. However, there is no report as to the modulatory effects of H 2 O 2 on interstitial cells of Cajal (ICC). We investigated the H 2 O 2 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. H 2 O 2 hyperpolarized the membrane and inhibited pacemaker currents. These effects were inhibited by glibenclamide, an inhibitor of ATP-sensitive K + (K ATP ) channels. The free-radical scavenger catalase inhibited the H 2 O 2 -induced effects. MAFP and AACOCF 3 (a cytosolic phospholipase A 2 inhibitors) or SC-560 and NS-398 (a selective COX-1 and 2 inhibitor) or AH6809 (an EP 2 receptor antagonist) inhibited the H 2 O 2 -induced effects. PD98059 (a mitogen activated/ERK-activating protein kinase inhibitor) inhibited the H 2 O 2 -induced effects, though SB-203580 (a p38 MAPK inhibitor) or a JNK inhibitor did not affect. H 2 O 2 -induced effects could not be inhibited by LY-294002 (an inhibitor of PI 3 -kinases), calphostin C (a protein kinase C inhibitor) or SQ-22536 (an adenylate cyclase inhibitor). Adenoviral infection analysis revealed H 2 O 2 stimulated tyrosine kinase activity and AG 1478 (an antagonist of epidermal growth factor receptor tyrosine kinase) inhibited the H 2 O 2 -induced effects. These results suggest H 2 O 2 can modulate ICC pacemaker activity and this occur by the activation of K ATP channels through PGE 2 production via receptor tyrosine kinase-dependent MAP kinase activation.

KW - Cyclooxygenase

KW - Hydrogen peroxide

KW - Interstitial cells of Cajal

KW - MAP kinase

KW - Pacemaker currents

KW - Receptor tyrosine kinase

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