Ethanol and its non-oxidative metabolites profoundly inhibit CFTR function in pancreatic epithelial cells which is prevented by ATP supplementation

Pflugers Archiv European Journal of Physiology

Volumn 466, Issue 3, 2014, Pages 549-562

  Judak L ^a   Hegyi, P ^a   Rakonczay, Z ^a   Maleth J ^a   Gray, M A ^b   Venglovecz, V ^a  

^a UNIVERSITY OF SZEGED   (Hungary)

^b NEWCASTLE UNIVERSITY   (United Kingdom)

Author keywords

Acute pancreatitis; ATP; CFTR; Ethanol; Fatty acids

Indexed keywords

ACETALDEHYDE; ADENOSINE TRIPHOSPHATE; ALCOHOL; CHLORIDE CHANNEL; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; FORSKOLIN; PALMITOLEIC ACID; PALMITOLEIC ACID ETHYL ESTER; UNCLASSIFIED DRUG;

ALCOHOL METABOLISM; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CHLORIDE CONDUCTANCE; CONTROLLED STUDY; EPITHELIUM CELL; EXPERIMENTAL GUINEA PIG; HUMAN; HUMAN CELL; METABOLITE; NONHUMAN; PANCREAS CELL; PANCREAS DUCT; PANCREATITIS; PRIORITY JOURNAL;

ACETALDEHYDE; ACTION POTENTIALS; ADENOSINE TRIPHOSPHATE; ANIMALS; CELL LINE, TUMOR; CELLS, CULTURED; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; EPITHELIAL CELLS; ETHANOL; FATTY ACIDS, MONOUNSATURATED; GUINEA PIGS; HUMANS; PANCREATIC DUCTS;

EID: 84896738968     PISSN: 00316768     EISSN: 14322013     Source Type: Journal    
DOI: 10.1007/s00424-013-1333-x     Document Type: Article

References (82)

1. Aleksandrov AA, Cui L, Riordan JR (2009) Relationship between nucleotide binding and ion channel gating in cystic fibrosis transmembrane conductance regulator. J Physiol 587:2875-86
2. Apte MV, Phillips PA, Fahmy RG, Darby SJ, Rodgers SC, McCaughan GW, Korsten MA, Pirola RC, Naidoo D, Wilson JS (2000) Does alcohol directly stimulate pancreatic fibrogenesis? Studies with rat pancreatic stellate cells. Gastroenterology 118:780-94
3. Apte MV, Pirola RC, Wilson JS (2005) Molecular mechanisms of alcoholic pancreatitis. Dig Dis 23:232-40
4. Apte MV, Wilson JS (2003) Stellate cell activation in alcoholic pancreatitis. Pancreas 27:316-20
5. Argent BE, Arkle S, Cullen MJ, Green R (1986) Morphological, biochemical and secretory studies on rat pancreatic ducts maintained in tissue culture. Q J Exp Physiol 71:633-48
6. Argent BE, Gray MA, Steward MC, Case RM (2006) Cell physiology of pancreatic ducts. In: Johnson LR (ed) Physiology of the gastrointestinal tract. Elsevier, San Diego, pp 1376-1396
7. Baggaley EM, Elliott AC, Bruce JI (2008) Oxidant-induced inhibition of the plasma membrane Ca2 + -ATPase in pancreatic acinar cells: role of the mitochondria. Am J Physiol Cell Physiol 295:C1247-60
8. Berger AL, Ikuma M, Welsh MJ (2005) Normal gating of CFTR requires ATP binding to both nucleotide-binding domains and hydrolysis at the second nucleotide-binding domain. Proc Natl Acad Sci U S A 102:455-60
9. Brooks PJ (2000) Brain atrophy and neuronal loss in alcoholism: a role for DNA damage? Neurochem Int 37:403-12
10. Cahill A, Hershman S, Davies A, Sykora P (2005) Ethanol feeding enhances age-related deterioration of the rat hepatic mitochondrion. Am J Physiol Gastrointest Liver Physiol 289:G1115-23
11. Chambers JA, Harris A (1993) Expression of the cystic fibrosis gene and the major pancreatic mucin gene, MUC1, in human ductal epithelial cells. J Cell Sci 105(Pt 2):417-22
12. Choudari CP, Lehman GA, Sherman S (1999) Pancreatitis and cystic fibrosis gene mutations. Gastroenterol Clin North Am 28:543-9, vii-viii
13. Cohn JA (2005) Reduced CFTR function and the pathobiology of idiopathic pancreatitis. J Clin Gastroenterol 39:S70-7
14. Cohn JA, Bornstein JD, Jowell PS (2000) Cystic fibrosis mutations and genetic predisposition to idiopathic chronic pancreatitis. Med Clin North Am 84:621-31, ix
15. Criddle DN, Raraty MG, Neoptolemos JP, Tepikin AV, Petersen OH, Sutton R (2004) Ethanol toxicity in pancreatic acinar cells: mediation by nonoxidative fatty acid metabolites. Proc Natl Acad Sci U S A 101:10738-43
16. Criddle DN, Murphy J, Fistetto G, Barrow S, Tepikin AV, Neoptolemos JP, Sutton R, Petersen OH (2006) Fatty acid ethyl esters cause pancreatic calcium toxicity via inositol trisphosphate receptors and loss of ATP synthesis. Gastroenterology 130:781-93
17. Diczfalusy MA, Bjorkhem I, Einarsson C, Hillebrant CG, Alexson SE (2001) Characterization of enzymes involved in formation of ethyl esters of long-chain fatty acids in humans. J Lipid Res 42:1025-32
18. Durbec JP, Sarles H (1978) Multicenter survey of the etiology of pancreatic diseases. Relationship between the relative risk of developing chronic pancreaitis and alcohol, protein and lipid consumption. Digestion 18:337-50
19. Durie PR (1998) Pancreatitis and mutations of the cystic fibrosis gene. N Engl J Med 339:687-8
20. Durie PR (1989) The pathophysiology of the pancreatic defect in cystic fibrosis. Acta Paediatr Scand Suppl 363:41-4
21. Frossard JL, Steer ML, Pastor CM (2008) Acute pancreatitis. Lancet 371:143-52
22. Furuno T, Kanno T, Arita K, Asami M, Utsumi T, Doi Y, Inoue M, Utsumi K (2001) Roles of long chain fatty acids and carnitine in mitochondrial membrane permeability transition. Biochem Pharmacol 62:1037-46
23. Gukovskaya AS, Mouria M, Gukovsky I, Reyes CN, Kasho VN, Faller LD, Pandol SJ (2002) Ethanol metabolism and transcription factor activation in pancreatic acinar cells in rats. Gastroenterology 122:106-18
24. Haber PS, Wilson JS, Apte MV, Pirola RC (1993) Fatty acid ethyl esters increase rat pancreatic lysosomal fragility. J Lab Clin Med 121:759-64
25. Haber PS, Apte MV, Applegate TL, Norton ID, Korsten MA, Pirola RC, Wilson JS (1998) Metabolism of ethanol by rat pancreatic acinar cells. J Lab Clin Med 132:294-302
26. Hamamoto T, Yamada S, Hirayama C (1990) Nonoxidative metabolism of ethanol in the pancreas; implication in alcoholic pancreatic damage. Biochem Pharmacol 39:241-5
27. Hegyi P, Maleth J, Venglovecz V, Rakonczay Z Jr (2011) Pancreatic ductal bicarbonate secretion: challenge of the acinar Acid load. Front Physiol 2:36
28. Hegyi P, Pandol S, Venglovecz V, Rakonczay Z Jr (2011) The acinar-ductal tango in the pathogenesis of acute pancreatitis. Gut 60:544-52
29. Hegyi P, Petersen O (2013) The exocrine pancreas: The acinar-ductal tango in physiology and pathophysiology. Rev Physiol Biochem Pharmacol. doi: 10.1007/112-2013-14
30. Hennager DJ, Ikuma M, Hoshi T, Welsh MJ (2001) A conditional probability analysis of cystic fibrosis transmembrane conductance regulator gating indicates that ATP has multiple effects during the gating cycle. Proc Natl Acad Sci U S A 98:3594-9
31. Hoffmeister A, Keim V (1999) CFTR mutations and chronic pancreatitis. Z Gastroenterol 37:1133-5
32. - channel by ATP-driven nucleotide-binding domain dimerisation. J Physiol 587:2151-61
33. - exchange activity in human pancreatic duct cells. Pancreas 38:921-9
34. Katz M, Carangelo R, Miller LJ, Gorelick F (1996) Effect of ethanol on cholecystokinin-stimulated zymogen conversion in pancreatic acinar cells. Am J Physiol 270:G171-5
35. Kostuch M, Rudzki S, Semczuk A, Kulczycki L (2002) CFTR gene mutations in patients suffering from acute pancreatitis. Med Sci Monit 8:BR369-72
36. Lamarche F, Carcenac C, Gonthier B, Cottet-Rousselle C, Chauvin C, Barret L, Leverve X, Savasta M, Fontaine E (2013) Mitochondrial permeability transition pore inhibitors prevent ethanol-induced neuronal death in mice. Chem Res Toxicol. doi: 10.1021/tx300395w
37. Lange LG (1991) Mechanism of fatty acid ethyl ester formation and biological significance. Ann N Y Acad Sci 625:802-5
38. Laposata EA, Lange LG (1986) Presence of nonoxidative ethanol metabolism in human organs commonly damaged by ethanol abuse. Science 231:497-9
39. Lee WK, Regan TJ (2002) Alcoholic cardiomyopathy: is it dose-dependent? Congest Heart Fail 8:303-6
40. Ma T, Thiagarajah JR, Yang H, Sonawane ND, Folli C, Galietta LJ, Verkman AS (2002) Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin-induced intestinal fluid secretion. J Clin Invest 110:1651-8
41. Majumdar AP, Vesenka GD, Dubick MA, Yu GS, DeMorrow JM, Geokas MC (1986) Morphological and biochemical changes of the pancreas in rats treated with acetaldehyde. Am J Physiol 250:G598-606
42. Maleth J, Venglovecz V, Razga Z, Tiszlavicz L, Rakonczay Z Jr, Hegyi P (2011) Non-conjugated chenodeoxycholate induces severe mitochondrial damage and inhibits bicarbonate transport in pancreatic duct cells. Gut 60:136-8
43. Maleth J, Rakonczay Z Jr, Venglovecz V, Dolman NJ, Hegyi P (2013) Central role of mitochondrial injury in the pathogenesis of acute pancreatitis. Acta Physiol (Oxf) 207:226-35
44. Mantle D, Falkous G, Peters TJ, Preedy VR (1999) Effect of ethanol and acetaldehyde on intracellular protease activities in human liver, brain and muscle tissues in vitro. Clin Chim Acta 281:101-8
45. McCarroll JA, Phillips PA, Park S, Doherty E, Pirola RC, Wilson JS, Apte MV (2003) Pancreatic stellate cell activation by ethanol and acetaldehyde: is it mediated by the mitogen-activated protein kinase signaling pathway? Pancreas 27:150-60
46. Muanprasat C, Sonawane ND, Salinas D, Taddei A, Galietta LJ, Verkman AS (2004) Discovery of glycine hydrazide pore-occluding CFTR inhibitors: mechanism, structure-activity analysis, and in vivo efficacy. J Gen Physiol 124:125-37
47. Murphy E, Steenbergen C, Levy LA, Raju B, London RE (1989) Cytosolic free magnesium levels in ischemic rat heart. J Biol Chem 264:5622-7
48. Neiman J (1998) Alcohol as a risk factor for brain damage: neurologic aspects. Alcohol Clin Exp Res 22:346S-351S
49. Niebergall-Roth E, Harder H, Singer MV (1998) A review: acute and chronic effects of ethanol and alcoholic beverages on the pancreatic exocrine secretion in vivo and in vitro. Alcohol Clin Exp Res 22:1570-83
50. O'Reilly CM, Winpenny JP, Argent BE, Gray MA (2000) Cystic fibrosis transmembrane conductance regulator currents in guinea pig pancreatic duct cells: inhibition by bicarbonate ions. Gastroenterology 118:1187-96
51. Pallagi P, Venglovecz V, Rakonczay Z Jr, Borka K, Korompay A, Ozsvari B, Judak L, Sahin-Toth M, Geisz A, Schnur A, Maleth J, Takacs T, Gray MA, Argent BE, Mayerle J, Lerch MM, Wittmann T, Hegyi P (2011) Trypsin reduces pancreatic ductal bicarbonate secretion by inhibiting CFTR Cl(-) channels and luminal anion exchangers. Gastroenterology 141:2228-2239
52. Pandol SJ, Periskic S, Gukovsky I, Zaninovic V, Jung Y, Zong Y, Solomon TE, Gukovskaya AS, Tsukamoto H (1999) Ethanol diet increases the sensitivity of rats to pancreatitis induced by cholecystokinin octapeptide. Gastroenterology 117:706-16
53. -]i and its role in pancreatic bicarbonate secretion. Gastroenterology 139:620-31
54. Peters-Golden M, Shelly C (1988) Inhibitory effect of exogenous arachidonic acid on alveolar macrophage 5-lipoxygenase metabolism. Role of ATP depletion J Immunol 140:1958-66
55. 2+ signal generation and pancreatitis. Cell Calcium 45:634-42
56. Pezzilli R, Morselli-Labate AM, Mantovani V, Romboli E, Selva P, Migliori M, Corinaldesi R, Gullo L (2003) Mutations of the CFTR gene in pancreatic disease. Pancreas 27:332-6
57. Ponnappa BC, Marciniak R, Schneider T, Hoek JB, Rubin E (1997) Ethanol consumption and susceptibility of the pancreas to cerulein-induced pancreatitis. Pancreas 14:150-7
58. Raju SV, Wang G (2012) Suppression of adenosine-activated chloride transport by ethanol in airway epithelia. PLoS One 7:e32112
59. Rakonczay Z Jr, Hegyi P, Hasegawa M, Inoue M, You J, Iida A, Ignath I, Alton EW, Griesenbach U, Ovari G, Vag J, Da Paula AC, Crawford RM, Varga G, Amaral MD, Mehta A, Lonovics J, Argent BE, Gray MA (2008) CFTR gene transfer to human cystic fibrosis pancreatic duct cells using a Sendai virus vector. J Cell Physiol 214:442-55
60. Ren CL (1999) Mutations of the cystic fibrosis gene and pancreatitis. N Engl J Med 340:238-9
61. Riley DJ, Kyger EM, Spilburg CA, Lange LG (1990) Pancreatic cholesterol esterases. 2. Purification and characterization of human pancreatic fatty acid ethyl ester synthase. Biochemistry 29:3848-52
62. Ronksley PE, Brien SE, Turner BJ, Mukamal KJ, Ghali WA (2011) Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis. BMJ 342:d671
63. Sankaran H, Lewin MB, Wong A, Deveney CW, Wendland MF, Leimgruber RM, Geokas MC (1985) Irreversible inhibition by acetaldehyde of cholecystokinin- induced amylase secretion from isolated rat pancreatic acini. Biochem Pharmacol 34:2859-63
64. Scheele GA, Fukuoka SI, Kern HF, Freedman SD (1996) Pancreatic dysfunction in cystic fibrosis occurs as a result of impairments in luminal pH, apical trafficking of zymogen granule membranes, and solubilization of secretory enzymes. Pancreas 12:1-9
65. Seitz HK, Stickel F (2007) Molecular mechanisms of alcohol-mediated carcinogenesis. Nat Rev Cancer 7:599-612
66. Sekimoto M, Takada T, Kawarada Y, Hirata K, Mayumi T, Yoshida M, Hirota M, Kimura Y, Takeda K, Isaji S, Koizumi M, Otsuki M, Matsuno S (2006) JPN guidelines for the management of acute pancreatitis: epidemiology, etiology, natural history, and outcome predictors in acute pancreatitis. J Hepatobiliary Pancreat Surg 13:10-24
67. Sharer N, Schwarz M, Malone G, Howarth A, Painter J, Super M, Braganza J (1998) Mutations of the cystic fibrosis gene in patients with chronic pancreatitis. N Engl J Med 339:645-52
68. Singh M, Simsek H (1990) Ethanol and the pancreas. Current status Gastroenterology 98:1051-62
69. Soderberg BL, Salem RO, Best CA, Cluette-Brown JE, Laposata M (2003) Fatty acid ethyl esters. Ethanol metabolites that reflect ethanol intake. Am J Clin Pathol 119(Suppl):S94-9
70. - secretion by mouse pancreatic duct. J Med Invest 56(Suppl):332-5
71. - secretion by guinea pig interlobular pancreatic duct. Am J Physiol Gastrointest Liver Physiol 296:G1307-17
72. Taylor CJ (1999) Chronic pancreatitis and mutations of the cystic fibrosis gene. Gut 44:8-9
73. Testino G (2008) Alcoholic diseases in hepato-gastroenterology: a point of view. Hepatogastroenterology 55:371-7
74. Tsujita T, Okuda H (1994) The synthesis of fatty acid ethyl ester by carboxylester lipase. Eur J Biochem 224:57-62
75. Venglovecz V, Rakonczay Z Jr, Ozsvari B, Takacs T, Lonovics J, Varro A, Gray MA, Argent BE, Hegyi P (2008) Effects of bile acids on pancreatic ductal bicarbonate secretion in guinea pig. Gut 57:1102-12
76. Venglovecz V, Hegyi P, Rakonczay Z Jr, Tiszlavicz L, Nardi A, Grunnet M, Gray MA (2011) Pathophysiological relevance of apical large-conductance Ca(2) + -activated potassium channels in pancreatic duct epithelial cells. Gut 60:361-9
77. Vergani P, Lockless SW, Nairn AC, Gadsby DC (2005) CFTR channel opening by ATP-driven tight dimerization of its nucleotide-binding domains. Nature 433:876-80
78. - secretion: relevance to cystic fibrosis. Embo J 25:5049-57
79. Werner J, Saghir M, Warshaw AL, Lewandrowski KB, Laposata M, Iozzo RV, Carter EA, Schatz RJ, Fernandez-Del Castillo C (2002) Alcoholic pancreatitis in rats: injury from nonoxidative metabolites of ethanol. Am J Physiol Gastrointest Liver Physiol 283:G65-73. doi: 10.1152/ajpgi.00419.2001
80. Wilson JS, Apte MV (2003) Role of alcohol metabolism in alcoholic pancreatitis. Pancreas 27:311-5
81. Yamamoto A, Ishiguro H, Ko SB, Suzuki A, Wang Y, Hamada H, Mizuno N, Kitagawa M, Hayakawa T, Naruse S (2003) Ethanol induces fluid hypersecretion from guinea-pig pancreatic duct cells. J Physiol 551:917-26
82. Yang SS, Huang CC, Chen JR, Chiu CL, Shieh MJ, Lin SJ, Yang SC (2005) Effects of ethanol on antioxidant capacity in isolated rat hepatocytes. World J Gastroenterol 11:7272-6