Mechanisms of damage of acinar pancreatic cells in acute alcohol pancreatitis
https://doi.org/10.29235/1814-6023-2019-16-1-108-116
Abstract
The review analyzes the current data on the main mechanisms of toxic effects of alcohol and its metabolites on pancreatic acinar cells in acute pancreatitis. It is shown that the mechanisms of cellular damage are multicomponent and closely linked by the regulatory factors of the molecular level. At the early stage of the disease, they lead to the following structural and functional changes in acinar cells that promote the premature intracellular trypsinogen activation and autoaggression: sustained rise of cytosolic Ca2+ and excess of mitochondrial matrix Ca2+; destabilization due to lysosomes and zymogen granules; debective autophagy; mitochondrial depolarization; decreased ATP production and necrosis.
About the Author
L. A. Mozheiko
Grodno State Medical University
Belarus
Belarus
Larisa A. Mozheiko – Ph. D. (Med.), Assistant Professor
80, Gorky Str., 230015, Grodno
References
1. Lysenko M., Devyatov A., Ursov S., Pas’ko V., Gritsyuk A. Acute pancreatitis. Differentiated diagnostic and treatment tactics. Moscow, Litterra Publ., 2010. 165 р. (in Russian).
2. Maev I. V., Kucheryavyi Yu. A. Diaseases of the pancreas. Vol. 2. Moscow, Meditsina Publ., 2008. 558 р. (in Russian).
3. Lankisch P. G., Apte M., Banks P. A. Acute pancreatitis. Gastroenterologiya Sankt-Peterburga [Gastroenterology of St. Petersburg], 2017, no. 2, рр. 3–13.
4. Gullo L., Migliori M., Olah A., Farkas G., Levy P., Arvanitakis C., Lankisch P., Beger H. Acute pancreatitis in fve european countries: etiology and mortality. Pancreas, 2002, vol. 24, no. 3, рр. 223–227. https://doi.org/10.1097/00006676-200204000-00003
5. Singh P., Garg P. K. Pathophysiological mechanisms in acute pancreatitis: current understanding. Indian Journal of Gastroenterology, 2016, vol. 35, no. 3, pp. 153–166. https://doi.org/10.1007/s12664-016-0647-y
6. Gryshchenko O., Gerasimenko J. V., Peng S., Gerasimenko O. V., Petersen O. H. Calcium signalling in the acinar environment of the exocrine pancreas: physiology and pathophysiology. Journal of Physiology, 2018, vol. 596, no. 14, рр. 2663– 2678. https://doi.org/10.1113/jp275395
7. Mukherjee R., Mareninova O. A., Odinokova I. V., Huang W., Murphy J., Chvanov M. [et al.]. Mechanism of mitochondrial permeability transition pore induction and damage in the pancreas: inhibition prevent acute pancreatitis by protecting production of ATP. Gut, 2015, vol. 65, no. 8, рр. 1333–1346. https://doi.org/10.1136/gutjnl-2014-308553
8. Gukovsky I., Pandol J. S., Gukovskaya A. S. Organellar dysfunction in the pathogenesis of pancreatitis. Antioxidants and Redox Signaling, 2011, vol. 15, no. 10, рр. 2699–2710. https://doi.org/10.1089/ars.2011.4068
9. Saluja A. K., Donovan E. A., Yamanaka K., Yamaguchi Y., Hofbauer B., Steer M. L. Caerulein-induced in vitro activation of trypsinogen in rat pancreatic acinus mediated by cathepsin B. Gastroenterology, 1997, vol. 113, рр. 304–310. https://doi.org/10.1016/s0016-5085(97)70108-2
10. Sherwood M. W., Prior I. A., Voronina S. G., Barrow S. L., Woodsmith J. D., Gerasimenko O. V., Petersen O. H., Tepikin A. V. Activation of trypsinogen in large endocytic vacuoles of pancreatic acinar cells. Proceeding of the National Academy of Sciences USA, 2007, vol. 104, no. 13, рр. 5674–5679. https://doi.org/10.1073/pnas.0700951104
11. Apte M. V., Wilson J. S., Korsten M. A., McCaughan G. W., Haber P. S., Pirola R. C. Effects of ethanol and protein defciency on pancreatic digestive and lysosomal enzymes. Gut, 1995, vol. 36, no. 2, рр. 287–293. https://doi.org/10.1136/gut.36.2.287
12. Mareninova O. A., Hermann K., French S. W., O’Konski M. S., Pandol S. J., Webster P., Erickson A. H., Katunuma N., Gorelick F. S., Gukovsky I., Gukovskaya A. S. Impaired autophagic flux mediates acinar cell vacuole formation and trypsinogen activation in rodent models of acute pancreatitis. Journal of Clinical Investigate, 2009, vol. 119, no. 11, рр. 3340–3355. https://doi.org/10.1172/jci38674
13. Song Z., Huang Y., Liu C., Lu M., Li Z., Sun B., Zhang W., Xue D. MiR-352 participates in the regulation of trypsinogen activation in pancreatic acinar cells by influencing the function of autophagic lysosomes. Oncotarget, 2018, vol. 9, no. 13, рр. 10868–10879. https://doi.org/10.18632/oncotarget.24220
14. Parzych K. R., Klionsky D. J. An overview of autophagy: morphology, mechanism, and regulation. Antioxidants and Redox Signaling, 2014, vol. 20, no. 3, рр. 460–473. https://doi.org/10.1089/ars.2013.5371
15. Helin H., Mero M., Markkula H., Helin M. Pancreatic acinar ultrastructure in human acute pancreatitis. Virchows Archiv A Pathological Anatomy and Histolology, 1980, vol. 387, no. 3, рр. 259–270. https://doi.org/10.1007/bf00454829
16. Niederau C., Grendell J. H. Intracellular vacuoles in experimental acute pancreatitis in rats and mice are an acidifd compartment. Journal Clinical Investigate, 1988, vol. 81, no. 1, рр. 229–236. https://doi.org/10.1172/jci113300
17. Raraty M., Ward J., Erdemli G., Vaillant C., Neoptolemos J. P., Sutton R., Petersen O. H. Calciumdependent enzyme activation and vacuole formation in the apical granular region of pancreatic acinar cells. Proceeding of the National Academy of Sciences USA, 2000, vol. 97, no. 24, рр. 13126–13131. https://doi.org/10.1073/pnas.97.24.13126
18. Klionsky D. J., Abeliovich H., Agostinis P., Agrawal D. K., Aliev G., Askew D. S. [et al.]. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy, 2008, vol. 4, рр. 151–175.
19. Nixon R. A., Yang D.-S., Lee J.-H. Neurodegenerative lysosomal disorders: a continuum from development to late age. Autophagy, 2008, vol. 4, no. 5, рр. 590–599. https://doi.org/10.4161/auto.6259
20. Eskelinen E.-L., Illert A. L., Tanaka Y., Schwarzmann G., Blanz J., Von Figura K., Saftig P. Role of LAMP-2 in lysosome biogenesis and autophagy. Molecular Biology of the Cell, 2002, vol. 13, no. 9, рр. 3355–3368. https://doi.org/10.1091/mbc.e02-02-0114
21. Huynh K. K., Eskelinen E.-L., Scott C. C., Malevanets A., Saftig P., Grinstein S. LAMP proteins are required for fusion of lysosomes with phagosomes. European Molecular Biology Organizatiion Journal, 2007, vol. 26, no. 2, рр. 313–324. https://doi.org/10.1038/sj.emboj.7601511
22. Levine B., Kroemer G. Autophagy in the pathogenesis of disease. Cell, 2008, vol. 132, no. 1, рр. 27–42. https://doi.org/10.1016/j.cell.2007.12.018
23. Fortunato F., Bürgers H., Bergmann F., Rieger P., Büchler M. W., Kroemer G., Werner J. Impaired autolysosome formation correlates with Lamp-2 depletion: role of apoptosis, autophagy, and necrosis in pancreatitis. Gastroenterology, 2009, vol. 137, no. 1, рр. 350–360.e5. https://doi.org/10.1053/j.gastro.2009.04.003
24. Gukovskaya A. S., Gukovsky I. Autophagy and pancreatitis. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2012, vol. 303, no. 9, рр. 993–1003. https://doi.org/10.1152/ajpgi.00122.2012
25. Gukovsky I., Li N., Todoric J., Gukovskaya A., Karin M. Inflammation, autophagy, and obesity: common features in the pathogenesis of pancreatitis and pancreatic cancer. Gastroenterology, 2013, vol. 144, no. 6, рр. 1199–1209.e4. https://doi.org/10.1053/j.gastro.2013.02.007
26. Waterford S. D., Kolodecik T. R., Thrower E. C., Gorelick F. S. Vacuolar ATPase regulates zymogen activation in pancreatic acini. Journal of Biological Chemistry, 2004, vol. 280, no. 7, рр. 5430–5434. https://doi.org/10.1074/jbc.m413513200
27. Czaja M. J. Functions of autophagy in hepatic and pancreatic physiology and disease. Gastroenterology, 2011, vol. 140, no. 7, рр. 1895–1908. https://doi.org/10.1053/j.gastro.2011.04.038
28. Whitcomb D. C., Gorry M. C., Preston R. A., Furey W., Sossenheimer M. J., Ulrich Ch. D., Martin S. P. [et al.]. Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nature Genetics, 1996, vol. 14, no. 2, рр. 141–145. https://doi.org/10.1038/ng1096-141
29. Petersen O. H., Tepikin A. V. Polarized calcium signaling in exocrine gland cells. Annual Review of Physiology, 2008, vol. 70, no. 1, рр. 273–299. https://doi.org/10.1146/annurev.physiol.70.113006.100618
30. Liang T., Dolai S., Xie L., Winter E., Orabi A. I., Karimian N., CosenBinker L. I., Huang Y.-C., Thorn P., Cattral M. S., Gaisano H. Y. Ex vivo human pancreatic slice preparations offer a valuable model for studying pancreatic exocrine biology. Journal of Biological Chemistry, 2017, vol. 292, no. 14, рр. 5957–5969. https://doi.org/10.1074/jbc.m117.777433
31. Ashby M. C., Camello-Almaraz C., Gerasimenko O. V., Petersen O. H., Tepikin A. V. Long-distance communication between muscarinic receptors and Ca2+ release channels revealed by carbachol uncaging in cell-attached patch pipette. Journal of Biological Chemistry, 2003, vol. 278, no. 23, рр. 20860–20864. https://doi.org/10.1074/jbc.m302599200
32. Berridge M. J. Inositol trisphosphate and calcium signaling. Nature, 1993, vol. 361, рр. 315–325.
33. Gerasimenko O. V., Gerasimenko J. V., Rizzuto R. R., Treiman M., Tepikin A. V., Petersen O. H. The distribution of the endoplasmic reticulum in living pancreatic acinar cells. Cell Calcium, 2002, vol. 32, no. 5–6, рр. 261–268. https://doi.org/10.1016/s0143416002001938
34. Lee M. G., Xu X., Zeng W. Z., Diaz J., Wojcikiewicz R. J. H., Kuo T. H., Wuytack F., Racymaekers L., Muallem S. Polarized expression of Ca2+ channels in pancreatic and salivary gland cells – correlation with initiation and propagation of [Ca2+] I waves. Journal of Biological Chemistry, 1997, vol. 272, no. 25, рр. 15765–15770. https://doi.org/10.1074/jbc.272.25.15765
35. Voronina S. G., Barrow S. L., Simpson A. W. M., Gerasimenko O. V., Da Silva Xavier G., Rutter G. A., Petersen O. H., Tepikin A. V. Dynamic changes in cytosolic and mitochondrial ATP levels in pancreatic acinar cells. Gastroenterology, 2010, vol. 138, no. 5, рр. 1976–1987.e5. https://doi.org/10.1053/j.gastro.2010.01.037
36. Gerasimenko J. V., Lur G., Sherwood M. W., Ebisui E., Tepikin A. V., Mikoshiba K., Gerasimenko O. V., Petersen O. H. Pancreatic protease activation by alcohol metabolite depends on Ca2+ release via acid store IP3 receptors. Proceeding of the National Academy of Sciences, 2009, vol. 106, no. 26, рр. 10758–10763. https://doi.org/10.1073/pnas.0904818106
37. Petersen O. H., Courjaret R., Machaca K. Ca2+ tunneling through the ER lumen as a mechanism for delivering Ca2+ entering via store-operated Ca2+ channels to specifc target sites. Journal of Physiology, 2017, vol. 595, no. 10, рр. 2999–3014. https://doi.org/10.1113/jp272772
38. Huang W., Booth D. M., Cane M. C., Chvanov M., Javed M. A., Elliott V. L. [et al.]. Fatty acid ethyl ester synthase inhibition ameliorates ethanol-induced Ca2+-dependent mitochondrial dysfunction and acute pancreatitis. Gut, 2013, vol. 63, no. 8, рр. 1313–1324. https://doi.org/10.1136/gutjnl-2012-304058
39. Gukovskaya A. S., Pandol S. J. Cell death pathways in pancreatitis and pancreatic cancer. Pancreatology, 2004, vol. 4, no. 6, рр. 567–586. https://doi.org/10.1159/000082182
40. Firsova V. G., Parshikov V. V., Kuznetsov S. S., Bugrova M. L., Yakovleva E. I. Acute pancreatitis: morphological aspects of the course of the disease. Annaly khirurgicheskoi gepatologii [Annals of surgical hepatology], 2014, vol. 19, no. 1, рр. 86–95 ( in Russian).
41. Thrower E. C., Gorelick F. S., Husainb S. Z. Molecular and cellular mechanisms of pancreatic injury. Current Opinion in Gastroenterology, 2010, vol. 26, no. 5, рр. 484–489. https://doi.org/10.1097/mog.0b013e32833d119e
42. Gerasimenko J. V., Gerasimenko O. V., Petersen O. H. The role of Ca2+ in the pathophysiology of pancreatitis. Journal of Physiology, 2013, vol. 592, no. 2, pp. 269–280. https://doi.org/10.1113/jphysiol.2013.261784
43. Rakonczay Z., Hegyi P., Takacs T., McCarroll J., Saluja A. K. The role of NF-kappa B activation in the pathogenesis of acute pancreatitis. Gut, 2007, vol. 57, no. 2, pp. 259–267. https://doi.org/10.1136/gut.2007.124115
Review
For citations:
Mozheiko L.A. Mechanisms of damage of acinar pancreatic cells in acute alcohol pancreatitis. Proceedings of the National Academy of Sciences of Belarus, Medical series. 2019;16(1):108-116. (In Russ.) https://doi.org/10.29235/1814-6023-2019-16-1-108-116
Views: 1733
Email this article 