Roles of connexins and pannexins in digestive homeostasis

Cellular and Molecular Life Sciences

Volumn 72, Issue 15, 2015, Pages 2809-2821

  Maes, Michaël ^a   Cogliati, Bruno ^b   Crespo Yanguas, Sara ^a   Willebrords, Joost ^a   Vinken, Mathieu ^a  

^a VRIJE UNIVERSITEIT BRUSSEL   (Belgium)

^b UNIVERSITY OF SÃO PAULO   (Brazil)

Author keywords

Connexin; Intestine; Liver; Pannexin; Physiology; Stomach

Indexed keywords

AMMONIA; CONNEXIN 26; CONNEXIN 31; CONNEXIN 32; CONNEXIN 36; CONNEXIN 37; CONNEXIN 40; CONNEXIN 43; CONNEXIN 45; CONNEXIN 57; GAP JUNCTION PROTEIN; PANNEXIN; PANNEXIN 1; PANNEXIN 2; UNCLASSIFIED DRUG;

ARTICLE; CELL COMMUNICATION; CELL MEMBRANE PERMEABILITY; CELLULAR DISTRIBUTION; CHANNEL GATING; COLON MOTILITY; CYTOSOL; DETOXIFICATION; DIGESTIVE SYSTEM; EXTRACELLULAR SPACE; GAP JUNCTION; GAP JUNCTIONAL INTERCELLULAR COMMUNICATION; GASTROINTESTINAL MOTILITY; GLYCOGENOLYSIS; HOMEOSTASIS; HUMAN; INNATE IMMUNITY; INTERSTITIAL CELL OF CAJAL; INTESTINE; INTRACELLULAR SIGNALING; LIVER; NONHUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN SYNTHESIS; STOMACH; STOMACH ACID SECRETION; TISSUE DISTRIBUTION; XENOBIOTIC METABOLISM; ANIMAL; DIGESTIVE FUNCTION; METABOLISM; PHYSIOLOGY;

ANIMALS; CELL COMMUNICATION; CONNEXINS; DIGESTIVE SYSTEM; DIGESTIVE SYSTEM PHYSIOLOGICAL PHENOMENA; GAP JUNCTIONS; HOMEOSTASIS; HUMANS;

EID: 84937725774     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-015-1961-8     Document Type: Article

References (161)

1. Alexander DB, Goldberg GS (2003) Transfer of biologically important molecules between cells through gap junction channels. Curr Med Chem 10(19):2045-2058
2. Dbouk HA, Mroue RM, El-Sabban ME, Talhouk RS (2009) Connexins: a myriad of functions extending beyond assembly of gap junction channels. Cell Commun Signal 7:4. doi: 10.1186/1478-811X-7-4
3. Decrock E, Vinken M, De Vuyst E, Krysko DV, D'Herde K, Vanhaecke T, Vandenabeele P, Rogiers V, Leybaert L (2009) Connexin-related signaling in cell death: to live or let die? Cell Death Differ 16(4):524-536. doi: 10.1038/cdd.2008.196
4. Loewenstein WR, Kanno Y (1967) Intercellular communication and tissue growth I. Cancerous growth. J Cell Biol 33(2):225-234
5. Revel JP, Karnovsky MJ (1967) Hexagonal array of subunits in intercellular junctions of the mouse heart and liver. J Cell Biol 33(3):C7-C12
6. Goodenough DA (1974) Bulk isolation of mouse hepatocyte gap junctions. Characterization of the principal protein, connexin. J Cell Biol 61(2):557-563
7. Paul DL (1986) Molecular cloning of cDNA for rat liver gap junction protein. J Cell Biol 103(1):123-134
8. Kumar NM, Gilula NB (1986) Cloning and characterization of human and rat liver cDNAs coding for a gap junction protein. J Cell Biol 103(3):767-776
9. Bai D, Wang AH (2014) Extracellular domains play different roles in gap junction formation and docking compatibility. Biochem J 458(1):1-10. doi: 10.1042/BJ20131162
10. Li Z, Zhou Z, Daniel EE (1993) Expression of gap junction connexin 43 and connexin 43 mRNA in different regional tissues of intestine in dog. Am J Physiol 265(5):G911-G916
11. Mikkelsen HB, Huizinga JD, Thuneberg L, Rumessen JJ (1993) Immunohistochemical localization of a gap junction protein (connexin43) in the muscularis externa of murine, canine, and human intestine. Cell Tissue Res 274(2):249-256
12. Panchin Y, Kelmanson I, Matz M, Lukyanov K, Usman N, Lukyanov S (2000) A ubiquitous family of putative gap junction molecules. Curr Biol 10(13):R473-R474
13. Wang N, De Bock M, Decrock E, Bol M, Gadicherla A, Vinken M, Rogiers V, Bukauskas FF, Bultynck G, Leybaert L (2013) Paracrine signaling through plasma membrane hemichannels. Biochim Biophys Acta 1828(1):35-50. doi: 10.1016/j.bbamem.2012.07.002
14. Diezmos EF, Sandow SL, Markus I, Shevy Perera D, Lubowski DZ, King DW, Bertrand PP, Liu L (2013) Expression and localization of pannexin-1 hemichannels in human colon in health and disease. Neurogastroenterol Motil 25(6):e395-e405. doi: 10.1111/nmo.12130
15. Le Vasseur M, Lelowski J, Bechberger JF, Sin WC, Naus CC (2014) Pannexin 2 protein expression is not restricted to the CNS. Front Cell Neurosci 8:392. doi: 10.3389/fncel.2014.00392
16. Bruzzone R, Hormuzdi SG, Barbe MT, Herb A, Monyer H (2003) Pannexins, a family of gap junction proteins expressed in brain. Proc Natl Acad Sci USA 100(23):13644-13649
17. Csak T, Ganz M, Pespisa J, Kodys K, Dolganiuc A, Szabo G (2011) Fatty acid and endotoxin activate inflammasomes in mouse hepatocytes that release danger signals to stimulate immune cells. Hepatology 54(1):133-144. doi: 10.1002/hep.24341
18. Ganz M, Csak T, Nath B, Szabo G (2011) Lipopolysaccharide induces and activates the Nalp3 inflammasome in the liver. World J Gastroenterol 17(43):4772-4778. doi: 10.3748/wjg.v17.i43.4772
19. Kim HY, Kim SJ, Lee SM (2015) Activation of NLRP3 and AIM2 inflammasomes in Kupffer cells in hepatic ischemia/reperfusion. FEBS J 282(2):259-270. doi: 10.1111/febs.13123
20. Xiao F, Waldrop SL, Khimji AK, Kilic G (2012) Pannexin1 contributes to pathophysiological ATP release in lipoapoptosis induced by saturated free fatty acids in liver cells. Am J Physiol Cell Physiol 303(10):C1034-C1044. doi: 10.1152/ajpcell.00175.2012
21. Li X, Cao J, Jin Q, Xie C, He Q, Cao R, Xiong J, Chen P, Wang X, Liang S (2008) A proteomic study reveals the diversified distribution of plasma membrane-associated proteins in rat hepatocytes. J Cell Biochem 104(3):965-984. doi: 10.1002/jcb.21680
22. Sáez PJ, Shoji KF, Aguirre A, Sáez JC (2014) Regulation of hemichannels and gap junction channels by cytokines in antigen-presenting cells. Mediators Inflamm 2014:742734. doi: 10.1155/2014/742734
23. Chandrasekhar A, Bera AK (2012) Hemichannels: permeants and their effect on development, physiology and death. Cell Biochem Funct 30(2):89-100
24. Spray DC, Ye ZC, Ransom BR (2006) Functional connexin "hemichannels": a critical appraisal. Glia 54(7):758-773
25. Harris AL (2007) Connexin channel permeability to cytoplasmic molecules. Prog Biophys Mol Biol 94(1-2):120-143. doi: 10.1016/j.pbiomolbio.2007.03.011
26. Guttman JA, Lin AE, Li Y, Bechberger J, Naus CC, Vogl AW, Finlay BB (2010) Gap junction hemichannels contribute to the generation of diarrhoea during infectious enteric disease. Gut 59(2):218-226. doi: 10.1136/gut.2008.170464
27. Simpson C, Kelsell DP, Marchès O (2013) Connexin 26 facilitates gastrointestinal bacterial infection in vitro. Cell Tissue Res 351(1):107-116. doi: 10.1007/s00441-012-1502-9
28. Tran Van Nhieu G, Clair C, Bruzzone R, Mesnil M, Sansonetti P, Combettes L (2003) Connexin-dependent inter-cellular communication increases invasion and dissemination of Shigella in epithelial cells. Nat Cell Biol 5(8):720-726. doi: 10.1038/ncb1021
29. Vinken M, Decrock E, De Vuyst E, De Bock M, Vandenbroucke RE, De Geest BG, Demeester J, Sanders NN, Vanhaecke T, Leybaert L, Rogiers V (2010) Connexin32 hemichannels contribute to the apoptotic-to-necrotic transition during Fas-mediated hepatocyte cell death. Cell Mol Life Sci 67(6):907-918. doi: 10.1007/s00018-009-0220-2
30. Vinken M, Decrock E, Vanhaecke T, Leybaert L, Rogiers V (2012) Connexin43 signaling contributes to spontaneous apoptosis in cultures of primary hepatocytes. Toxicol Sci 125(1):175-186. doi: 10.1093/toxsci/kfr277
31. Liu X, Furuya T, Li D, Xu J, Cao X, Li Q, Xu Z, Sasaki K (2010) Connexin 26 expression correlates with less aggressive phenotype of intestinal type-gastric carcinomas. Int J Mol Med 25(5):709-716
32. Fiertak A, Semik D, Kilarski WM (1999) Immunohistochemical analysis of connexin26 and 43 expression in the mouse alimentary tract. Folia Biol (Krakow) 47(1):5-11
33. Zhang JT, Nicholson BJ (1989) Sequence and tissue distribution of a second protein of hepatic gap junctions, Cx26, as deduced from its cDNA. J Cell Biol 109(6):3391-3401
34. Radebold K, Horakova E, Gloeckner J, Ortega G, Spray DC, Vieweger H, Siebert K, Manuelidis L, Geibel JP (2001) Gap junctional channels regulate acid secretion in the mammalian gastric gland. J Membr Biol 183(3):147-153
35. Uchida Y, Matsuda K, Sasahara K, Kawabata H, Nishioka M (1995) Immunohistochemistry of gap junctions in normal and diseased gastric mucosa of humans. Gastroenterology 109(5):1492-1496
36. Mine T, Yusuda H, Kataoka A, Tajima A, Nagasawa J, Takano T (1995) Human chronic gastric ulcer and connexin. J Clin Gastroenterol 21(Suppl 1):S104-S107
37. Ohkusa T, Fujiki K, Tamura Y, Yamamoto M, Kyoi T (1995) Freeze-fracture and immunohistochemical studies of gap junctions in human gastric mucosa with special reference to their relationship to gastric ulcer and gastric carcinoma. Microsc Res Tech 31(3):226-233. doi: 10.1002/jemt.1070310306
38. Wu J, Zhou HF, Wang CH, Zhang B, Liu D, Wang W, Sui GJ (2007) Decreased expression of Cx32 and Cx43 and their function of gap junction intercellular communication in gastric cancer. Zhonghua Zhong Liu Za Zhi 29(10):742-747
39. Hertzberg EL, Skibbens RV (1984) A protein homologous to the 27,000 dalton liver gap junction protein is present in a wide variety of species and tissues. Cell 39(1):61-69
40. Iwata F, Joh T, Ueda F, Yokoyama Y, Itoh M (1998) Role of gap junctions in inhibiting ischemia-reperfusion injury of rat gastric mucosa. Am J Physiol 275(5):G883-G888
41. Kyoi T, Ueda F, Kimura K, Yamamoto M, Kataoka K (1992) Development of gap junctions between gastric surface mucous cells during cell maturation in rats. Gastroenterology 102(6):1930-1935
42. Takahashi N, Joh T, Yokoyama Y, Seno K, Nomura T, Ohara H, Ueda F, Itoh M (2000) Importance of gap junction in gastric mucosal restitution from acid-induced injury. J Lab Clin Med 136(2):93-99. doi: 10.1067/mlc.2000.108158
43. Fink C, Hembes T, Brehm R, Weigel R, Heeb C, Pfarrer C, Bergmann M, Kressin M (2006) Specific localisation of gap junction protein connexin 32 in the gastric mucosa of horses. Histochem Cell Biol 125(3):307-313. doi: 10.1007/s00418-005-0047-3
44. Nishitani A, Hirota S, Nishida T, Isozaki K, Hashimoto K, Nakagomi N, Matsuda H (2005) Differential expression of connexin 43 in gastrointestinal stromal tumours of gastric and small intestinal origin. J Pathol 206(4):377-382. doi: 10.1002/path.1799
45. Seki K, Komuro T (2002) Distribution of interstitial cells of Cajal and gap junction protein, Cx 43 in the stomach of wild-type and W/Wv mutant mice. Anat Embryol (Berl) 206(1):57-65. doi: 10.1007/s00429-002-0279-0
46. Dupont E, el Aoumari A, Roustiau-Sévère S, Briand JP, Gros D (1988) Immunological characterization of rat cardiac gap junctions: presence of common antigenic determinants in heart of other vertebrate species and in various organs. J Membr Biol 104(2):119-128
47. Kadle R, Zhang JT, Nicholson BJ (1991) Tissue-specific distribution of differentially phosphorylated forms of Cx43. Mol Cell Biol 11(1):363-369
48. Mitsui R, Komuro T (2002) Direct and indirect innervation of smooth muscle cells of rat stomach, with special reference to the interstitial cells of Cajal. Cell Tissue Res 309(2):219-227. doi: 10.1007/s00441-002-0592-1
49. Wang YF, Daniel EE (2001) Gap junctions in gastrointestinal muscle contain multiple connexins. Am J Physiol Gastrointest Liver Physiol 281(2):G533-G543
50. Larson DM, Gilbert RJ, Beyer EC (1992) Two-dimensional coupling by gap junctions in cultured gastric smooth muscle monolayers. Am J Physiol 263(2):G261-G268
51. Cousins HM, Edwards FR, Hickey H, Hill CE, Hirst GD (2003) Electrical coupling between the myenteric interstitial cells of Cajal and adjacent muscle layers in the Guinea-pig gastric antrum. J Physiol 550(3):829-844. doi: 10.1113/jphysiol.2003.042176
52. Iino S, Asamoto K, Nojyo Y (2001) Heterogeneous distribution of a gap junction protein, connexin43, in the gastroduodenal junction of the Guinea pig. Auton Neurosci 93(1):8-13. doi: 10.1016/S1566-0702(01)00320-4
53. Seki K, Zhou DS, Komuro T (1998) Immunohistochemical study of the c-kit expressing cells and connexin 43 in the Guinea-pig digestive tract. J Auton Nerv Syst 68(3):182-187
54. Daniel EE, Sakai Y, Fox JE, Posey-Daniel V (1984) Structural basis for function of circular muscle of canine corpus. Can J Physiol Pharmacol 62(10):1304-1314
55. Faussone-Pellegrini MS, Pantalone D, Cortesini C (1989) An ultrastructural study of the interstitial cells of Cajal of the human stomach. J Submicrosc Cytol Pathol 21(3):439-460
56. Daniel EE, Berezin I, Allescher HD, Manaka H, Posey-Daniel V (1989) Morphology of the canine pyloric sphincter in relation to function. Can J Physiol Pharmacol 67(12):1560-1573
57. Powley TL, Wang XY, Fox EA, Phillips RJ, Liu LW, Huizinga JD (2008) Ultrastructural evidence for communication between intramuscular vagal mechanoreceptors and interstitial cells of Cajal in the rat fundus. Neurogastroenterol Motil 20(1):69-79. doi: 10.1111/j.1365-2982.2007.00990.x
58. Bracken S, Byrne G, Kelly J, Jackson J, Feighery C (2008) Altered gene expression in highly purified enterocytes from patients with active coeliac disease. BMC Genom 9:377. doi: 10.1186/1471-2164-9-377
59. Clair C, Combettes L, Pierre F, Sansonetti P, Tran Van Nhieu G (2008) Extracellular-loop peptide antibodies reveal a predominant hemichannel organization of connexins in polarized intestinal cells. Exp Cell Res 314(6):1250-1265. doi: 10.1016/j.yexcr.2007.12.021
60. Frinchi M, Di Liberto V, Turimella S, D'Antoni F, Theis M, Belluardo N, Mudò G (2013) Connexin36 (Cx36) expression and protein detection in the mouse carotid body and myenteric plexus. Acta Histochem 115(3):252-256. doi: 10.1016/j.acthis.2012.07.005
61. Husøy T, Ølstørn HB, Knutsen HK, Løberg EM, Cruciani V, Mikalsen SO, Goverud IL, Alexander J (2004) Truncated mouse adenomatous polyposis coli reduces connexin32 content and increases matrilysin secretion from Paneth cells. Eur J Cancer 40(10):1599-1603. doi: 10.1016/j.ejca.2004.02.024
62. Leaphart CL, Qureshi F, Cetin S, Li J, Dubowski T, Baty C, Batey C, Beer-Stolz D, Guo F, Murray SA, Hackam DJ (2007) Interferon-gamma inhibits intestinal restitution by preventing gap junction communication between enterocytes. Gastroenterology 132(7):2395-2411. doi: 10.1053/j.gastro.2007.03.029
63. Manthey D, Bukauskas F, Lee CG, Kozak CA, Willecke K (1999) Molecular cloning and functional expression of the mouse gap junction gene connexin-57 in human HeLa cells. J Biol Chem 274(21):14716-14723
64. + dendritic cells. Immunity 40(2):248-261. doi: 10.1016/j.immuni.2013.12.012
65. Nakamura K, Kuraoka A, Kawabuchi M, Shibata Y (1998) Specific localization of gap junction protein, connexin45, in the deep muscular plexus of dog and rat small intestine. Cell Tissue Res 292(3):487-494
66. Nemeth L, Maddur S, Puri P (2000) Immunolocalization of the gap junction protein Connexin43 in the interstitial cells of Cajal in the normal and Hirschsprung's disease bowel. J Pediatr Surg 35(6):823-828. doi: 10.1053/jpsu.2000.6851
67. Seki K, Komuro T (2001) Immunocytochemical demonstration of the gap junction proteins connexin 43 and connexin 45 in the musculature of the rat small intestine. Cell Tissue Res 306(3):417-422. doi: 10.1007/s00441-001-0470-2
68. Willecke K, Heynkes R, Dahl E, Stutenkemper R, Hennemann H, Jungbluth S, Suchyna T, Nicholson BJ (1991) Mouse connexin37: cloning and functional expression of a gap junction gene highly expressed in lung. J Cell Biol 114(5):1049-1057
69. Gumber S, Nusrat A, Villinger F (2014) Immunohistological characterization of intercellular junction proteins in rhesus macaque intestine. Exp Toxicol Pathol 66(9):437-444. doi: 10.1016/j.etp.2014.07.004
70. Dubina MV, Iatckii NA, Popov DE, Vasil'ev SV, Krutovskikh VA (2002) Connexin 43, but not connexin 32, is mutated at advanced stages of human sporadic colon cancer. Oncogene 21(32):4992-4996. doi: 10.1038/sj.onc.1205630
71. Ennes HS, Young SH, Goliger JA, Mayer EA (1999) Chemical signaling from colonic smooth muscle cells to DRG neurons in culture. Am J Physiol 276(3):C602-C610
72. Han Y, Zhang PJ, Chen T, Yum SW, Pasha T, Furth EE (2011) Connexin43 expression increases in the epithelium and stroma along the colonic neoplastic progression pathway: implications for its oncogenic role. Gastroenterol Res Pract 2011:561719. doi: 10.1155/2011/561719
73. Ismail R, Rashid R, Andrabi K, Parray FQ, Besina S, Shah MA, Ul Hussain M (2014) Pathological implications of Cx43 down-regulation in human colon cancer. Asian Pac J Cancer Prev 15(7):2987-2991
74. Kanczuga-Koda L, Sulkowski S, Koda M, Skrzydlewska E, Sulkowska M (2005) Connexin 26 correlates with Bcl-xL and Bax proteins expression in colorectal cancer. World J Gastroenterol 11(10):1544-1548
75. Mattii L, Ippolito C, Segnani C, Battolla B, Colucci R, Dolfi A, Bassotti G, Blandizzi C, Bernardini N (2013) Altered expression pattern of molecular factors involved in colonic smooth muscle functions: an immunohistochemical study in patients with diverticular disease. PLoS One 8(2):e57023. doi: 10.1371/journal.pone.0057023
76. 2+ responses in enteric glia are mediated by connexin-43 hemichannels and modulate colonic transit in mice. Gastroenterology 146(2):497-507. doi: 10.1053/j.gastro.2013.10.061
77. Sedhom MA, Pichery M, Murdoch JR, Foligné B, Ortega N, Normand S, Mertz K, Sanmugalingam D, Brault L, Grandjean T, Lefrancais E, Fallon PG, Quesniaux V, Peyrin-Biroulet L, Cathomas G, Junt T, Chamaillard M, Girard JP, Ryffel B (2013) Neutralisation of the interleukin-33/ST2 pathway ameliorates experimental colitis through enhancement of mucosal healing in mice. Gut 62(12):1714-1723. doi: 10.1136/gutjnl-2011-301785
78. Sirnes S, Honne H, Ahmed D, Danielsen SA, Rognum TO, Meling GI, Leithe E, Rivedal E, Lothe RA, Lind GE (2011) DNA methylation analyses of the connexin gene family reveal silencing of GJC1 (Connexin45) by promoter hypermethylation in colorectal cancer. Epigenetics 6(5):602-609
79. Sirnes S, Bruun J, Kolberg M, Kjenseth A, Lind GE, Svindland A, Brech A, Nesbakken A, Lothe RA, Leithe E, Rivedal E (2012) Connexin43 acts as a colorectal cancer tumor suppressor and predicts disease outcome. Int J Cancer 131(3):570-581. doi: 10.1002/ijc.26392
80. Daniel EE, Thomas J, Ramnarain M, Bowes TJ, Jury J (2001) Do gap junctions couple interstitial cells of Cajal pacing and neurotransmission to gastrointestinal smooth muscle? Neurogastroenterol Motil 13(4):297-307
81. Daniel EE, Yazbi AE, Mannarino M, Galante G, Boddy G, Livergant J, Oskouei TE (2007) Do gap junctions play a role in nerve transmissions as well as pacing in mouse intestine? Am J Physiol Gastrointest Liver Physiol 292(3):G734-G745. doi: 10.1152/ajpgi.00428.2006
82. Eugenin EA, Gonzalez HE, Sanchez HA, Branes MC, Saez JC (2007) Inflammatory conditions induce gap junctional communication between rat Kupffer cells both in vivo and in vitro. Cell Immunol 247(2):103-110
83. Fischer R, Reinehr R, Lu TP, Schonicke A, Warskulat U, Dienes HP, Haussinger D (2005) Intercellular communication via gap junctions in activated rat hepatic stellate cells. Gastroenterology 128(2):433-448
84. Gonzalez HE, Eugenin EA, Garces G, Solis N, Pizarro M, Accatino L, Saez JC (2002) Regulation of hepatic connexins in cholestasis: possible involvement of Kupffer cells and inflammatory mediators. Am J Physiol Gastrointest Liver Physiol 282(6):G991-G1001
85. Hernández-Guerra M, González-Méndez Y, de Ganzo ZA, Salido E, García-Pagán JC, Abrante B, Malagón AM, Bosch J, Quintero E (2014) Role of gap junctions modulating hepatic vascular tone in cirrhosis. Liver Int 34(6):859-868. doi: 10.1111/liv.12446
86. Chaytor AT, Martin PE, Edwards DH, Griffith TM (2001) Gap junctional communication underpins EDHF-type relaxations evoked by ACh in the rat hepatic artery. Am J Physiol Heart Circ Physiol 280(6):H2441-H2450
87. Shiojiri N, Niwa T, Sugiyama Y, Koike T (2006) Preferential expression of connexin37 and connexin40 in the endothelium of the portal veins during mouse liver development. Cell Tissue Res 324(3):547-552. doi: 10.1007/s00441-006-0165-9
88. Spray DC, Saez JC, Hertzberg EL, Dermietzel R (1994) Gap junctions in liver: composition, function, and regulation. In: Arias IM, Boyer JL, Fausto N, Jakoby DA, Schachter DA, Shaftrits DA (eds) The liver: biology and pathobiology. Raven Press, New York, pp 951-967
89. Berthoud VM, Iwanij V, Garcia AM, Sáez JC (1992) Connexins and glucagon receptors during development of rat hepatic acinus. Am J Physiol 263(5):G650-G658
90. Iwai M, Harada Y, Muramatsu A, Tanaka S, Mori T, Okanoue T, Katoh F, Ohkusa T, Kashima K (2000) Development of gap junctional channels and intercellular communication in rat liver during ontogenesis. J Hepatol 32(1):11-18. doi: 10.1016/s0168-8278(00)80184-1
91. Kojima T, Kokai Y, Chiba H, Yamamoto M, Mochizuki Y, Sawada N (2001) Cx32 but not Cx26 is associated with tight junctions in primary cultures of rat hepatocytes. Exp Cell Res 263(2):193-201. doi: 10.1006/excr.2000.5103
92. Fowler SL, Akins M, Zhou H, Figeys D, Bennett SA (2013) The liver connexin32 interactome is a novel plasma membrane-mitochondrial signaling nexus. J Proteome Res 12(6):2597-2610. doi: 10.1021/pr301166p
93. Oyamada M, Takebe K, Oyamada Y (2012) Regulation of connexin expression by transcription factors and epigenetic mechanisms. Biochim Biophys Acta 1828(1):118-133. doi: 10.1016/j.bbamem.2011.12.031
94. Koffler LD, Fernstrom MJ, Akiyama TE, Gonzalez FJ, Ruch RJ (2002) Positive regulation of connexin32 transcription by hepatocyte nuclear factor-1alpha. Arch Biochem Biophys 407(2):160-167
95. Piechocki MP, Burk RD, Ruch RJ (1999) Regulation of connexin32 and connexin43 gene expression by DNA methylation in rat liver cells. Carcinogenesis 20(3):401-406
96. Vinken M, Henkens T, Vanhaecke T, Papeleu P, Geerts A, Van Rossen E, Chipman JK, Meda P, Rogiers V (2006) Trichostatin a enhances gap junctional intercellular communication in primary cultures of adult rat hepatocytes. Toxicol Sci 91(2):484-492. doi: 10.1093/toxsci/kfj152
97. Klotz LO (2012) Posttranscriptional regulation of connexin-43 expression. Arch Biochem Biophys 524(1):23-29. doi: 10.1016/j.abb.2012.03.012
98. Johnstone SR, Billaud M, Lohman AW, Taddeo EP, Isakson BE (2012) Posttranslational modifications in connexins and pannexins. J Membr Biol 245(5):319-332. doi: 10.1007/s00232-012-9453-3
99. Saez JC, Spray DC, Nairn AC, Hertzberg E, Greengard P, Bennett MV (1986) cAMP increases junctional conductance and stimulates phosphorylation of the 27-kDa principal gap junction polypeptide. Proc Natl Acad Sci USA 83(8):2473-2477
100. Elvira M, Díez JA, Wang KK, Villalobo A (1993) Phosphorylation of connexin-32 by protein kinase C prevents its proteolysis by mu-calpain and m-calpain. J Biol Chem 268(19):14294-14300
101. Fukushi Y, Sakurai T, Terakawa S (2014) Cell-to-cell propagation of intracellular signals fluorescently visualized with acridine orange in the gastric glands of Guinea pigs. Biochem Biophys Res Commun 447(1):38-43. doi: 10.1016/j.bbrc.2014.03.095
102. Ueda F, Kyoi T, Mimura K, Kimura K, Yamamoto M (1991) Intercellular communication in cultured rabbit gastric epithelial cells. Jpn J Pharmacol 57(3):321-328
103. Ueda F, Kameda Y, Yamamoto O, Shibata Y (1994) Beta-adrenergic regulation of gap-junctional intercellular communication in cultured rabbit gastric epithelial cells. J Pharmacol Exp Ther 271(1):397-402
104. Endo K, Watanabe S, Nagahara A, Hirose M, Sato N (1995) Restoration of gap junctions in the regenerative process of ethanol-induced gastric mucosal injury. J Gastroenterol Hepatol 10(5):589-594
105. Mine T, Kushima R, Fujita T (1997) Relationship between healing of acetic acid-induced chronic gastric ulcer and connexin. J Clin Gastroenterol 25(Suppl 1):S111-S115
106. Saund RS, Kanai-Azuma M, Kanai Y, Kim I, Lucero MT, Saijoh Y (2012) Gut endoderm is involved in the transfer of left-right asymmetry from the node to the lateral plate mesoderm in the mouse embryo. Development 139(13):2426-2435. doi: 10.1242/dev.079921
107. Viotti M, Niu L, Shi SH, Hadjantonakis AK (2012) Role of the gut endoderm in relaying left-right patterning in mice. PLoS Biol 10(3):e1001276. doi: 10.1371/journal.pbio.1001276
108. Morita H, Katsuno T, Hoshimoto A, Hirano N, Saito Y, Suzuki Y (2004) Connexin 26-mediated gap junctional intercellular communication suppresses paracellular permeability of human intestinal epithelial cell monolayers. Exp Cell Res 298(1):1-8. doi: 10.1016/j.yexcr.2004.03.046
109. Sibaev A, Yüce B, Schirra J, Göke B, Allescher HD, Storr M (2006) Are gap junctions truly involved in inhibitory neuromuscular interaction in mouse proximal colon? Clin Exp Pharmacol Physiol 33(8):740-745. doi: 10.1111/j.1440-1681.2006.04433.x
110. Daniel EE, Wang YF (1999) Gap junctions in intestinal smooth muscle and interstitial cells of Cajal. Microsc Res Tech 47(5):309-320
111. Döring B, Pfitzer G, Adam B, Liebregts T, Eckardt D, Holtmann G, Hofmann F, Feil S, Feil R, Willecke K (2007) Ablation of connexin43 in smooth muscle cells of the mouse intestine: functional insights into physiology and morphology. Cell Tissue Res 327(2):333-342. doi: 10.1007/s00441-006-0281-6
112. Nagy JI, Urena-Ramirez V, Ghia JE (2014) Functional alterations in gut contractility after connexin36 ablation and evidence for gap junctions forming electrical synapses between nitrergic enteric neurons. FEBS Lett 588(8):1480-1490. doi: 10.1016/j.febslet.2014.02.002
113. Ey B, Eyking A, Gerken G, Podolsky DK, Cario E (2009) TLR2 mediates gap junctional intercellular communication through connexin-43 in intestinal epithelial barrier injury. J Biol Chem 284(33):22332-22343. doi: 10.1074/jbc.M901619200
114. Simon AM, McWhorter AR (2002) Vascular abnormalities in mice lacking the endothelial gap junction proteins connexin37 and connexin40. Dev Biol 251(2):206-220
115. Naves MMV, Silveira ER, Dagli MLZ, Moreno FS (2001) Effects of beta-carotene and vitamin A on oval cell proliferation and connexin 43 expression during hepatic differentiation in the rat. J Nutr Biochem 12(12):685-692. doi: 10.1016/s0955-2863(01)00187-5
116. Neveu MJ, Hully JR, Babcock KL, Vaughan J, Hertzberg EL, Nicholson BJ, Paul DL, Pitot HC (1995) Proliferation-associated differences in the spatial and temporal expression of gap junction genes in rat liver. Hepatology 22(1):202-212
117. Paku S, Nagy P, Kopper L, Thorgeirsson SS (2004) 2-acetylaminofluorene dose-dependent differentiation of rat oval cells into hepatocytes: confocal and electron microscopic studies. Hepatology 39(5):1353-1361. doi: 10.1002/hep.20178
118. Kojima T, Mitaka T, Shibata Y, Mochizuki Y (1995) Induction and regulation of connexin26 by glucagon in primary cultures of adult rat hepatocytes. J Cell Sci 108(8):2771-2780
119. Saez JC, Berthoud VM, Branes MC, Martinez AD, Beyer EC (2003) Plasma membrane channels formed by connexins: their regulation and functions. Physiol Rev 83(4):1359-1400. doi: 10.1152/physrev.00007.2003
120. Stumpel F, Ott T, Willecke K, Jungermann K (1998) Connexin 32 gap junctions enhance stimulation of glucose output by glucagon and noradrenaline in mouse liver. Hepatology 28(6):1616-1620. doi: 10.1002/hep.510280622
121. Clair C, Chalumeau C, Tordjmann T, Poggioli J, Erneux C, Dupont G, Combettes L (2001) Investigation of the roles of Ca(2+) and InsP(3) diffusion in the coordination of Ca(2+) signals between connected hepatocytes. J Cell Sci 114:1999-2007
122. Nelles E, Butzler C, Jung D, Temme A, Gabriel HD, Dahl U, Traub O, Stumpel F, Jungermann K, Zielasek J, Toyka KV, Dermietzel R, Willecke K (1996) Defective propagation of signals generated by sympathetic nerve stimulation in the liver of connexin32-deficient mice. Proc Natl Acad Sci USA 93(18):9565-9570. doi: 10.1073/pnas.93.18.9565
123. Bode HP, Wang L, Cassio D, Leite MF, St-Pierre MV, Hirata K, Okazaki K, Sears ML, Meda P, Nathanson MH, Dufour JF (2002) Expression and regulation of gap junctions in rat cholangiocytes. Hepatology 36(3):631-640. doi: 10.1053/jhep.2002.35274
124. Nathanson MH, Rios-Velez L, Burgstahler AD, Mennone A (1999) Communication via gap junctions modulates bile secretion in the isolated perfused rat liver. Gastroenterology 116(5):1176-1183. doi: 10.1016/s0016-5085(99)70021-1
125. Neveu MJ, Babcock KL, Hertzberg EL, Paul DL, Nicholson BJ, Pitot HC (1994) Colocalized alterations in connexin32 and cytochrome P450IIB1/2 by phenobarbital and related liver tumor promoters. Cancer Res 54(12):3145-3152
126. Shoda T, Mitsumori K, Onodera H, Toyoda K, Uneyama C, Imazawa T, Hirose M (1999) The relationship between decrease in Cx32 and induction of P450 isozymes in the early phase of clofibrate hepatocarcinogenesis in the rat. Arch Toxicol 73(7):373-380
127. Shoda T, Mitsumori K, Onodera H, Toyoda K, Uneyama C, Takada K, Hirose M (2000) Liver tumor-promoting effect of beta-naphthoflavone, a strong CYP 1A1/2 inducer, and the relationship between CYP 1A1/2 induction and Cx32 decrease in its hepatocarcinogenesis in the rat. Toxicol Pathol 28(4):540-547
128. Yang J, Ichikawa A, Tsuchiya T (2003) A novel function of connexin 32: marked enhancement of liver function in a hepatoma cell line. Biochem Biophys Res Commun 307(1):80-85
129. Fladmark KE, Gjertsen BT, Molven A, Mellgren G, Vintermyr OK, Døskeland SO (1997) Gap junctions and growth control in liver regeneration and in isolated rat hepatocytes. Hepatology 25(4):847-855. doi: 10.1002/hep.510250411
130. Kren BT, Kumar NM, Wang SQ, Gilula NB, Steer CJ (1993) Differential regulation of multiple gap junction transcripts and proteins during rat liver regeneration. J Cell Biol 123(3):707-718
131. Temme A, Ott T, Dombrowski F, Willecke K (2000) The extent of synchronous initiation and termination of DNA synthesis in regenerating mouse liver is dependent on connexin32 expressing gap junctions. J Hepatol 32(4):627-635
132. Kojima T, Yamamoto T, Murata M, Lan M, Takano K, Go M, Ichimiya S, Chiba H, Sawada N (2003) Role of the p38 MAP-kinase signaling pathway for Cx32 and claudin-1 in the rat liver. Cell Commun Adhes 10(4-6):437-443
133. Chipman JK, Mally A, Edwards GO (2003) Disruption of gap junctions in toxicity and carcinogenicity. Toxicol Sci 71(2):146-153
134. Koffler L, Roshong S, Park IK, Cesen-Cummings K, Thompson DC, Dwyer-Nield LD, Rice P, Mamay C, Malkinson AM, Ruch RJ (2000) Growth inhibition in G(1) and altered expression of cyclin D1 and p27(kip-1) after forced connexin expression in lung and liver carcinoma cells. J Cell Biochem 79(3):347-354
135. Yano T, Hernandez-Blazquez FJ, Omori Y, Yamasaki H (2001) Reduction of malignant phenotype of HEPG2 cell is associated with the expression of connexin 26 but not connexin 32. Carcinogenesis 22(10):1593-1600. doi: 10.1093/carcin/22.10.1593
136. Wilson MR, Close TW, Trosko JE (2000) Cell population dynamics (apoptosis, mitosis, and cell-cell communication) during disruption of homeostasis. Exp Cell Res 254(2):257-268
137. Vinken M, Maes M, Cavill R, Valkenborg D, Ellis JK, Decrock E, Leybaert L, Staes A, Gevaert K, Oliveira AG, Menezes GB, Cogliati B, Dagli ML, Ebbels TM, Witters E, Keun HC, Vanhaecke T, Rogiers V (2013) Proteomic and metabolomic responses to connexin43 silencing in primary hepatocyte cultures. Arch Toxicol 87(5):883-894. doi: 10.1007/s00204-012-0994-0
138. Azarashvili T, Baburina Y, Grachev D, Krestinina O, Evtodienko Y, Stricker R, Reiser G (2011) Calcium-induced permeability transition in rat brain mitochondria is promoted by carbenoxolone through targeting connexin43. Am J Physiol Cell Physiol 300(3):C707-C720. doi: 10.1152/ajpcell.00061.2010
139. Goubaeva F, Mikami M, Giardina S, Ding B, Abe J, Yang J (2007) Cardiac mitochondrial connexin 43 regulates apoptosis. Biochem Biophys Res Commun 352(1):97-103
140. Lu G, Haider HKh, Porollo A, Ashraf M (2010) Mitochondria-specific transgenic overexpression of connexin-43 simulates preconditioning-induced cytoprotection of stem cells. Cardiovasc Res 88(2):277-286. doi: 10.1093/cvr/cvq293
141. Chekeni FB, Elliott MR, Sandilos JK, Walk SF, Kinchen JM, Lazarowski ER, Armstrong AJ, Penuela S, Laird DW, Salvesen GS, Isakson BE, Bayliss DA, Ravichandran KS (2010) Pannexin 1 channels mediate 'find-me' signal release and membrane permeability during apoptosis. Nature 467(7317):863-867
142. Qu Y, Misaghi S, Newton K, Gilmour LL, Louie S, Cupp JE, Dubyak GR, Hackos D, Dixit VM (2011) Pannexin-1 is required for ATP release during apoptosis but not for inflammasome activation. J Immunol 186(11):6553-6561
143. Sandilos JK, Chiu YH, Chekeni FB, Armstrong AJ, Walk SF, Ravichandran KS, Bayliss DA (2012) Pannexin 1, an ATP release channel, is activated by caspase cleavage of its pore-associated c-terminal autoinhibitory region. J Biol Chem 287(14):11303-11311. doi: 10.1074/jbc.M111.323378
144. Iglesias R, Locovei S, Roque A, Alberto AP, Dahl G, Spray DC, Scemes E (2008) P2X(7) receptor-Pannexin1 complex: pharmacology and signaling. Am J Physiol Cell Physiol 295(3):C752-C760. doi: 10.1152/ajpcell.00228.2008
145. Pelegrin P, Surprenant A (2006) Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. EMBO J 25(21):5071-5082
146. Pelegrin P, Surprenant A (2007) Pannexin-1 couples to maitotoxin- and nigericin-induced interleukin-1beta release through a dye uptake-independent pathway. J Biol Chem 282(4):2386-2394
147. Bodendiek SB, Raman G (2010) Connexin modulators and their potential targets under the magnifying glass. Curr Med Chem 17(34):4191-4230
148. Abudara V, Bechberger J, Freitas-Andrade M, De Bock M, Wang N, Bultynck G, Naus CC, Leybaert L, Giaume C (2014) The connexin43 mimetic peptide Gap19 inhibits hemichannels without altering gap junctional communication in astrocytes. Front Cell Neurosci 8:306. doi: 10.3389/fncel.2014.00306
149. Iyyathurai J, Dhondt C, Wang N, De Bock M, Himpens B, Retamal MA, Stehberg J, Leybaert L, Bultynck G (2013) Peptides and peptide-derived molecules targeting the intracellular domains of Cx43: gap junctions versus hemichannels. Neuropharmacology 75:491-505. doi: 10.1016/j.neuropharm.2013.04.050
150. Pelegrin P, Barroso-Gutierrez C, Surprenant A (2008) P2X7 receptor differentially couples to distinct release pathways for IL-1beta in mouse macrophage. J Immunol 180(11):7147-7157
151. Kanczuga-Koda L, Sulkowski S, Koda M, Sobaniec-Lotowska M, Sulkowska M (2004) Expression of connexins 26, 32 and 43 in the human colon: an immunohistochemical study. Folia Histochem Cytobiol 42(4):203-207
152. Nicholson B, Dermietzel R, Teplow D, Traub O, Willecke K, Revel JP (1987) Two homologous protein components of hepatic gap junctions. Nature 329(6141):732-734. doi: 10.1038/329732a0
153. Kuraoka A, Iida H, Hatae T, Shibata Y, Itoh M, Kurita T (1993) Localization of gap junction proteins, connexins 32 and 26, in rat and Guinea pig liver as revealed by quick-freeze, deep-etch immunoelectron microscopy. J Histochem Cytochem 41(7):971-980
154. Nakashima Y, Ono T, Yamanoi A, El-Assal ON, Kohno H, Nagasue N (2004) Expression of gap junction protein connexin32 in chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. J Gastroenterol 39(8):763-768
155. Temme A, Traub O, Willecke K (1998) Downregulation of connexin32 protein and gap-junctional intercellular communication by cytokine-mediated acute-phase response in immortalized mouse hepatocytes. Cell Tissue Res 294(2):345-350
156. Tang B, Peng ZH, Yu PW, Yu G, Qian F, Zeng DZ, Zhao YL, Shi Y, Hao YX, Luo HX (2013) Aberrant expression of Cx43 is associated with the peritoneal metastasis of gastric cancer and Cx43-mediated gap junction enhances gastric cancer cell diapedesis from peritoneal mesothelium. PLoS ONE 8(9):e74527. doi: 10.1371/journal.pone.0074527
157. Oyamada M, Krutovskikh VA, Mesnil M, Partensky C, Berger F, Yamasaki H (1990) Aberrant expression of gap junction gene in primary human hepatocellular carcinomas: increased expression of cardiac-type gap junction gene connexin 43. Mol Carcinog 3(5):273-278
158. Wang ZS, Wu LQ, Yi X, Geng C, Li YJ, Yao RY (2013) Connexin-43 can delay early recurrence and metastasis in patients with hepatitis B-related hepatocellular carcinoma and low serum alpha-fetoprotein after radical hepatectomy. BMC Cancer 13:306. doi: 10.1186/1471-2407-13-306
159. Zhang D, Kaneda M, Nakahama K, Arii S, Morita I (2007) Connexin 43 expression promotes malignancy of HuH7 hepatocellular carcinoma cells via the inhibition of cell-cell communication. Cancer Lett 252(2):208-215. doi: 10.1016/j.canlet.2006.12.024
160. Balasubramaniyan V, Dhar DK, Warner AE, Vivien Li WY, Amiri AF, Bright B, Mookerjee RP, Davies NA, Becker DL, Jalan R (2013) Importance of Connexin-43 based gap junction in cirrhosis and acute-on-chronic liver failure. J Hepatol 58(6):1194-1200. doi: 10.1016/j.jhep.2013.01.023
161. Cogliati B, Da Silva TC, Aloia TP, Chaible LM, Real-Lima MA, Sanches DS, Matsuzaki P, Hernandez-Blazquez FJ, Dagli ML (2011) Morphological and molecular pathology of CCL4-induced hepatic fibrosis in connexin43-deficient mice. Microsc Res Tech 74(5):421-429. doi: 10.1002/jemt.20926