Receptor tyrosine and MAP kinase are involved in effects of H2O2 on interstitial cells of Cajal in murine intestine
Seok Choi
Department of Physiology, College of Medicine, Chosun University, Gwangju, Korea
Search for more papers by this authorCheol Ho Yeum
Department of Physiology, College of Medicine, Chosun University, Gwangju, Korea
Search for more papers by this authorYoung Dae Kim
Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Korea
Search for more papers by this authorChan Guk Park
Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Korea
Search for more papers by this authorMan Yoo Kim
Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Korea
Search for more papers by this authorJong-Seong Park
Department of Physiology, Chonnam National University Medical School, Gwangju, Korea
Search for more papers by this authorHan-Seong Jeong
Department of Physiology, Chonnam National University Medical School, Gwangju, Korea
Search for more papers by this authorByung Joo Kim
Department of Physiology and Biophysics, College of Medicine, Seoul National University, Seoul, Korea
Search for more papers by this authorInsuk So
Department of Physiology and Biophysics, College of Medicine, Seoul National University, Seoul, Korea
Search for more papers by this authorKi Whan Kim
Department of Physiology and Biophysics, College of Medicine, Seoul National University, Seoul, Korea
Search for more papers by this authorCorresponding Author
Jae Yeoul Jun
Department of Physiology and Biophysics, College of Medicine, Seoul National University, Seoul, Korea
Correspondence to: Jae Yeoul JUN, M.D., Ph.D., Department of Physiology, College of Medicine, Chosun University, Sesuk-dong, Dongku, 501-375, Gwanju, Korea.Tel.: +82-62-230-6412Fax: +82-62-232-4943E-mail: [email protected]Search for more papers by this authorSeok Choi
Department of Physiology, College of Medicine, Chosun University, Gwangju, Korea
Search for more papers by this authorCheol Ho Yeum
Department of Physiology, College of Medicine, Chosun University, Gwangju, Korea
Search for more papers by this authorYoung Dae Kim
Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Korea
Search for more papers by this authorChan Guk Park
Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Korea
Search for more papers by this authorMan Yoo Kim
Department of Internal Medicine, College of Medicine, Chosun University, Gwangju, Korea
Search for more papers by this authorJong-Seong Park
Department of Physiology, Chonnam National University Medical School, Gwangju, Korea
Search for more papers by this authorHan-Seong Jeong
Department of Physiology, Chonnam National University Medical School, Gwangju, Korea
Search for more papers by this authorByung Joo Kim
Department of Physiology and Biophysics, College of Medicine, Seoul National University, Seoul, Korea
Search for more papers by this authorInsuk So
Department of Physiology and Biophysics, College of Medicine, Seoul National University, Seoul, Korea
Search for more papers by this authorKi Whan Kim
Department of Physiology and Biophysics, College of Medicine, Seoul National University, Seoul, Korea
Search for more papers by this authorCorresponding Author
Jae Yeoul Jun
Department of Physiology and Biophysics, College of Medicine, Seoul National University, Seoul, Korea
Correspondence to: Jae Yeoul JUN, M.D., Ph.D., Department of Physiology, College of Medicine, Chosun University, Sesuk-dong, Dongku, 501-375, Gwanju, Korea.Tel.: +82-62-230-6412Fax: +82-62-232-4943E-mail: [email protected]Search for more papers by this authorAbstract
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.
References
- 1 Reddy SN, Bazzocchi G, Chan S, et al . Colonic motility and transit in health and ulcerative colitis. Gastroenterology. 1991; 101: 1289–97.
- 2 Vrees MD, Pricolo VE, Potenti FM, et al. Abnormal motility in patients with ulcerative colitis: the role of inflammatory cytokines. Arch Surg. 2002; 137: 439–45.
- 3 Myers BS, Martin JS, Dempsey DT, et al. Acute experimental colitis decreases colonic circular smooth muscle contractility in rats. Am J Physiol. 1997; 273: G928–36.
- 4 Goldhill JM, Sanders KM, Sjogren R, et al. Changes in enteric neural regulation of smooth muscle in a rabbit model of small intestinal inflammation. Am J Physiol. 1995; 268: G823–30.
- 5 Blennerhassett MG, Vignjevic P, Vermillion DL, et al. Inflammation causes hyperplasia and hypertrophy in smooth muscle of rat small intestine. Am J Physiol. 1992; 262: G1041–6.
- 6 Ozaki H, Hori M, Kinoshita K, et al . Intestinal dysmotility in inflammatory bowel disease: mechanisms of the reduced activity of smooth muscle contraction. Inflammopharmacology. 2005; 13: 103–11.
- 7 Grisham MB. Oxidants and free radicals in inflammatory bowel disease. Lancet. 1994; 344: 859–61.
- 8 Cao W, Vrees MD, Potenti FM, et al. Interleukin 1beta-induced production of H2O2 contributes to reduced sigmoid colonic circular smooth muscle contractility in ulcerative colitis. J Pharmacol Exp Ther. 2004; 311: 60–70.
- 9 Cao W, Fiocchi C, Pricolo VE. Production of IL-1beta, hydrogen peroxide, and nitric oxide by colonic mucosa decreases sigmoid smooth muscle contractility in ulcerative colitis. Am J Physiol Cell Physiol. 2005; 289: C1408–16.
- 10 Cheng L, Harnett KM, Cao W, et al. Hydrogen peroxide reduces lower esophageal sphincter tone in human esophagitis. Gastroenterology. 2005; 129: 1675–85.
- 11 Ward SM, Burns AJ, Torihashi S, et al. Mutation of the proto-oncogene c-kit blocks development of interstitial cells and electrical rhythmicity in murine intestine. J Physiol. 1994; 480: 91–7.
- 12 Huizinga JD, Thuneberg L, Kluppel M, et al. W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature. 1995; 373: 347–9.
- 13 Thomsen L, Robinson TL, Lee JC, et al. Interstitial cells of Cajal generate a rhythmic pacemaker current. Nat Med. 1998; 4: 848–51.
- 14 Daniel EE, Willis A, Cho WJ, et al. Comparisons of neural and pacing activities in intestinal segment for W/W++ and W/Wv mice. Neurogastroenterol Motil. 2005; 17: 355–65.
- 15 Yin J, Hou X, Chen JDZ. Roles of interstitial cells of Cajal in intestinal transit and exogenous electrical pacing. Dig Dis Sci. 2006; 51: 1818–23.
- 16 Faussone-Pellegrini MS. Relationships between neurokinin receptor-expressing interstitial cells of Cajal and tachykininergic nerves in the gut. J Cell Mol Med. 2006; 10: 20–32.
- 17 Ward SM, Sanders KM, Hirst GD. Role of interstitial cells of Cajal in neural control of gastrointestinal smooth muscles. Neurogastroenterol Motil. 2004; 16: 112–7.
- 18 Lu G, Qian X, Berezin I, et al. Inflammation modulates in vitro colonic myoelectric and contractile activity and interstitial cells of Cajal. Am J Physiol. 1997; 273: G1233–45.
- 19 Koh SD, Sanders KM, Ward SM. Spontaneous electrical rhythmicity in cultured interstitial cells of Cajal from the murine small intestine. J Physiol. 1998; 513: 203–13.
- 20 Choi S, Yeum CH, Chang IY, et al. Activating of ATP-dependent K+ channels comprised of Kir 6.2 and SUR 2B by PGE2 through EP2 receptor in cultured interstitial cells of Cajal from murine small intestine. Cell Physiol Biochem. 2006; 18: 187–98.
- 21 Lu G, Mazet B, Sun C, et al. Inflammatory modulation of calcium-activated potassium channels in canine colonic circular smooth muscle cells. Gastroenterology. 1999; 116: 884–92.
- 22 Prasad M, Goyal RK. Differential modulation of voltage-dependent K+ currents in colonic smooth muscle by oxidants. Am J Physiol Cell Physiol. 2004; 286: C671–82.
- 23 Jun JY, Choi S, Chang IY, et al. Deoxycholic acid inhibits pacemaker currents by activating ATP-dependent K+ channels through prostaglandin E2 in interstitial cells of Cajal from the murine small intestine. Br J Pharmacol. 2005; 144: 242–51.
- 24 Choi S, Park CG, Kim MY, et al. Action of imipramine on activated ATP-sensitive K+ channels in interstitial cells of Cajal from murine small intestine. Life Sci. 2006; 78: 2322–8.
- 25 Xiao ZL, Andrada MJ, Biancani P, et al. Reactive oxygen species (H2O2): effects on the gallbladder muscle of guinea pigs. Am J Physiol Gastrointest Liver Physiol. 2002; 282: G300–6.
- 26 Cao W, Cheng L, Behar J, et al. IL-1 beta signaling in Cat Lower Esophageal Sphincter (LES) Circular Muscle. Am J Physiol Gastrointest Liver Physiol. 2006; 291: G672–80.
- 27 Narumiya S, Sugimoto Y, Ushikubi F. Prostanoid receptors: structures, properties, and functions. Physiol Rev. 1999; 79: 1193–226.
- 28 Cao W, Sohn UD, Bitar KN, et al. MAPK mediates PKC-dependent contraction of cat esophageal and lower esophageal sphincter circular smooth muscle. Am J Physiol Gastrointest Liver Physiol. 2003; 285: G86–95.
- 29 Pearson G, Robinson F, Beers Gibson T, et al. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001; 22: 153–83.
- 30 Zhang J, Jin N, Liu Y, et al. Hydrogen peroxide stimulates extracellular signal-regulated protein kinases in pulmonary arterial smooth muscle cells. Am J Respir Cell Mol Biol. 1998; 19: 324–32.
- 31 Abe MK, Kartha S, Karpova AY, et al. Hydrogen peroxide activates extracellular signal-regulated kinase via protein kinase C, Raf-1, and MEK1. Am J Respir Cell Mol Biol. 1998; 18: 562–9.
- 32 Tabet F, Schiffrin EL, Touyz RM. Mitogen-activated protein kinase activation by hydrogen peroxide is mediated through tyrosine kinase-dependent, protein kinase C-independent pathways in vascular smooth muscle cells: upregulation in spontaneously hypertensive rats. J Hypertens. 2005; 23: 2005–12.
- 33 Song HJ, Lee TS, Jeong JH, et al. Hydrogen peroxide-induced extracellular signal-regulated kinase activation in cultured feline ileal smooth muscle cells. J Pharmacol Exp Ther. 2005; 312: 391–8.
- 34 Lin YF, Raab-Graham K, Jan YN, et al. NO stimulation of ATP-sensitive potassium channels: involvement of Ras/mitogen-activated protein kinase pathway and contribution to neuroprotection. Proc Natl Acad Sci USA. 2004; 101: 7799–804.
- 35 Pai R, Soreghan B, Szabo IL, et al. Prostaglandin E2 transactivates EGF receptor: a novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy. Nat Med. 2002; 8: 289–93.
- 36 Jabbour HN, Boddy SC. Prostaglandin E2 induces proliferation of glandular epithelial cells of the human endometrium via extracellular regulated kinase 1/2-mediated pathway. J Clin Endocrinol Metab. 2003; 88: 4481–7.
- 37 Stork PJ, Schmitt JM. Crosstalk between cAMP and MAP kinase signaling in the regulation of cell proliferation. Trends Cell Biol. 2002; 12: 258–66.
- 38 Sanders KM. G protein-coupled receptors in gastrointestinal physiology. IV. Neural regulation of gastrointestinal smooth muscle. Am J Physiol. 1998; 275: G1–7.
- 39 Zhang L, Bonev AD, Mawe GM, et al. Protein kinase A mediates activation of ATP-sensitive K+ currents by CGRP in gallbladder smooth muscle. Am J Physiol. 1994; 267: G494–9.
- 40 Jun JY, Choi S, Yeum CH, et al. Noradrenaline inhibits pacemaker currents through stimulation of beta 1-adrenoceptors in cultured interstitial cells of Cajal from murine small intestine. Br J Pharmacol. 2004; 141: 670–7.
- 41 Yang ZW, Zheng T, Wang J, et al. Hydrogen peroxide induces contraction and raises [Ca2+]i in canine cerebral arterial smooth muscle: participation of cellular signaling pathways. Naunyn Schmiedebergs Arch Pharmacol. 1999; 360: 646–53.
- 42 Cross DA, Alessi DR, Vandenheede JR, et al. The inhibition of glycogen synthase kinase-3 by insulin or insulin-like growth factor 1 in the rat skeletal muscle cell line L6 is blocked by wortmannin, but not by rapamycin: evidence that wortmannin blocks activation of the mitogen-activated protein kinase pathway in L6 cells between Ras and Raf. Biochem J. 1994; 303: 21–6.
- 43 Hawes BE, Luttrell LM, Van Biesen T, et al. Phosphatidylinositol 3-kinase is an early intermediate in the G beta gamma-mediated mitogen-activated protein kinase signaling pathway. J Biol Chem. 1996; 271: 12133–6.
- 44 Cao W, Sohn UD, Bitar KN, et al. MAPK mediates PKC-dependent contraction of cat esophageal and lower esophageal sphincter circular smooth muscle. Am J Physiol Gastrointest Liver Physiol. 2003; 285: G86–95.
- 45 Polosukhina D, Singaravelu K, Padanilam BJ. Activation of protein kinase C isozymes protects LLCPK1 cells from H2O2 induced necrotic cell death. Am J Nephrol. 2003; 23: 380–9.
- 46 Shimojima N, Nakaki T, Morikawa Y, et al. Imatinib blocks spontaneous mechanical activities in the adult mouse small intestine: possible inhibition of c-Kit signaling. Pharmacology. 2005; 74: 95–9.
- 47 Popescu LM, Vidulescu C, Curici A, et al. Imatinib inhibits spontaneous rhythmic contractions of human uterus and intestine. Eur J Pharmacol. 2006; 546: 177–81.
- 48 Hackel PO, Zwick E, Prenzel N, et al. Epidermal growth factor receptors: critical mediators of multiple receptor pathways. Curr Opin Cell Biol. 1999; 11: 184–9.
- 49 Luttrell LM, Daaka Y, Lefkowitz RJ. Regulation of tyrosine kinase cascades by G-protein-coupled receptors. Curr Opin Cell Biol. 1999; 11: 177–83.
- 50 Kataoka K, Takikawa Y, Lin SD, et al . Prostaglandin E2 receptor EP4 agonist induces Bcl-xL and independently activates proliferation signals in mouse primary hepatocytes. J Gastroenterol. 2005; 40: 610–6.
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