Necrotizing Pancreatitis: the Basic Pathways of Cell Death and Its Possible Clinical Value

Abstract


The basic pathways of cell death in acute pancreatitis are reviewed. The variants of apoptosis and its phases are analyzed. The value of cell death receptor complex is estimated. The role of caspases and other molecular regulation structures are defined. The value of necrosis and apoptosis in severe acute pancreatitis is measured. Is showed than both processes are dependent on intercellular and intracellular signals, ATP level and expression of regulator proteins. The protective impact of caspase cascade to the cell necrosis is underlined. Data about negative prognostic value of necrosis and positive influence of apoptosis in context of cell death type in severe acute pancreatitis are reflected. The particularity of autophagy and its variants are presented. The morphological changes of pancreatocytes are described. Based on the analysis of publications the authors conclude that the processes responsible for the death of cells are multicomponent, have different levels of regulation and in some cases are linked by common factors of molecular level. Development of medical treatment methods aimed at blocking any single mechanism cannot produce the desired effect. The possible prospects based on fundamental researches aimed at altering the expression of regulatory genes related to inflammation, apoptosis, and necrosis.

Nizhny Novgorod State Medical Academy, Russian Federation, Nizhny Novgorod, Russian Federation

Author for correspondence.
Email: author@vestnik-surgery.com
surgeon of the City hospital № 35 of Nizhny Novgorod

Nizhny Novgorod state Medical academy, russian Federation, Nizhny Novgorod, Russian Federation

Email: author@vestnik-surgery.com
Doctor of Medicine, Professor of the Department of hospital surgery named after B.A. Korolev of Nizhny Novgorod State Medical Academy

  1. Gordeeva a.V., Labas iu.a., Zviagil'skaia r.a. apoptoz odnokletochnyh organizmov: mekhanizmy i ehvolyuciya. [apoptosis of single-celled organisms: mechanisms and evolution]. Biokhimiia, 2004; 10(69): 1301-1313. - (in russian).
  2. Gostishchev V.k., khrupkin V.i., afanas'ev a.N. i dr. Lechebno-diagnosticheskaya taktika pri ostrom destruktivnom pankreatite v zavisimosti ot proizvoditel'nosti integral'nyh shkal tyazhesti. [Medical-diagnostic tactics in acute destructive pancreatitis depending on the performance of integrated scales of severity]. Materialy VII Vserossiiskoi konferencii obshchikh khirurgov s mezhdunarodnym uchastiem [Proc. 7th allrussian conference of general surgeons with international participation]. krasnoiarsk, 2012; 66-71. - (in russian).
  3. savel'ev V.s., Filimonov M.i., Burnevich s.Z. Pankreonekrozy [Necrotizing pancreatitis]. Moscow,
  4. Meditsinskoe informatsionnoe agentstvo, 2008; 264 p. - (in russian).
  5. Tolstoi a.D. Ostryi pankreatit. Trudnosti, vozmozhnosti, perspektivy. Klinicheskie lektsii [acute pancreatitis. Difficulties, opportunities and prospects]. saint-Petersburg. Predpriiatie sPb soiuza khudozhnikov, 1997; 140 p. - (in russian).
  6. Banks r.a., Martin L. Freeman M.L. Prakticheskie rekomendacii pri ostrom pankreatite. [Practice guidelines in acute pancreatitis]. Am. J. Gastroenterol., 2006; 101: 2379–2400.
  7. Bhatia M. apoptoz pankreaticheskih acinarnyh kletok pri ostrom pankreatite: ehto horosho ili ploho? [apoptosis of pancreatic acinar cells in acute pancreatitis: is it good or bad]? J. Cell. Mol. Med., 2004; 8(3): 402-409.
  8. Bhatia M. apoptoz protiv nekroza pri ostrom pankreatite. [apoptosis versus necrosis in acute pancreatitis]. Am. J. Physiol. Gastrointest. Liver Physiol., 2004; 286(2): 189-196.
  9. Bradley E.L. sistemy klinicheski na osnove klassifikacii ostrogo pankreatita. rezyume mezhdunarodnogo simpoziuma po ostromu pankreatit. [a clinically based classification system for acute pancreatitis. summary of the international symposium on acute pancreatitis]. (atlanta, 1992). Arch. Surg., 1993; 128: 586–590.
  10. Chan F.k., shisler J., Bixby J.G. et al. rol' nekroza opuholi, receptor-2 faktora i receptor-vzaimodejstvuyushchego belka v zaprogrammirovannyj nekroz i protivovirusnyh otvetov. [a role for tumor necrosis factor receptor-2 and receptor-interacting protein in programmed necrosis and antiviral responses]. J. Biol. Chem., 2003; 278(51): 51613-51621.
  11. Cohen G.M. Kaspazy: karateli apoptoza. [Caspases: the executioners of apoptosis]. Biochem. J., 1997; 326: 1-16.
  12. Criddle D.N., Gerasimenko J.V., Baumgartner h.k. et al. Signalizaciya kal'ciya i podzheludochnoj kletochnaya smert': apoptoz ili nekroz? [Calcium signalling and pancreatic cell death: apoptosis or necrosis]? Cell Death Differ., 2007; 14(7): 1285-1294.
  13. Czaja M.J. Funkcii autofagii v pecheni i podzheludochnoj fiziologii i boleznej. [Functions of autophagy in hepatic and pancreatic physiology and disease]. Gastroenterology, 2011; 140(7): 1895-1908.
  14. Danial N.N., korsmeyer s.J. Smert' kletki: kriticheskie kontrol'nye tochki. [Cell death: critical control points]. Cell, 2004; 116(2): 205-19.
  15. Edinger a.L., Thompson C.B. Smert' po dizajnu: apoptoza, nekroza i autofagii. [Death by design: apoptosis, necrosis and autophagy]. Curr. Opin. Cell Biol., 2004; 16(6): 663-669.
  16. Feng D., Park o., radaeva s. et al. interlejkin-22 uluchshaet "cerulein"-inducirovannogo pankreatita u myshej putem ingibirovaniya puti autofagii. [interleukin-22 ameliorates cerulein-induced pancreatitis in mice by inhibiting the autophagic pathway]. Int. J. Biol. Sci., 2012; 8(2): 249-257.
  17. Festjens N., Vanden Berghe T., Vandenabeele P. Necrosis, horosho srezhissirovannyj forma kletochnoj gibeli: signal'nye kaskady, vazhnyh posrednikov i soputstvuyushchej immunnyj otvet. [a well-orchestrated form of cell demise: signalling cascades, important mediators and concomitant immune response]. Biochim, Biophys. Acta., 2006; 1757(9-10): 1371-1387.
  18. Fortunato F., Deng X., Gates L.k. et al. Pankreaticheskij otvet na ehndotoksin posle hronicheskogo vozdejstviya alkogolya: perekhodit' ot apoptoza k nekrozu. [Pancreatic response to endotoxin after chronic alcohol exposure: switch from apoptosis to necrosis]? Am. J. Physiol. Gastrointest. Liver Physiol., 2006; 290(2): 232-241.
  19. Gukovskaya a.s., Gukovsky i., Jung Y. et al. Holecistokinin vyzyvaet aktivaciyu kaspaz i mitohondrial'noj disfunkcii v pankreaticheskih acinarnyh kletok. roli v processah povrezhdeniya kletok pankreatita.[Cholecystokinin induces caspase activation and mitochondrial dysfunction in pancreatic acinar cells. roles in cell injury processes of pancreatitis]. J. Biol. Chem., 2002; 277(25): 22595-22604.
  20. Gukovskaya a.s., Pandol s.J. Puti gibeli kletok pri pankreatite i rake podzheludochnoj zhelezy. [Cell death pathways in pancreatitis and pancreatic cancer]. Pancreatology, 2004; 4(6): 567-86.
  21. Gukovskaya a.s., Perkins P., Zaninovic V. et al. Mekhanizmy kletochnoj gibeli posle zakuporki protoka podzheludochnoj zhelezy v opossumov i krys. [Mechanisms of cell death after pancreatic duct obstruction in the opossum and the rat]. Gastroenterology, 1996; 110(3): 875-884.
  22. Gukovsky i., Pandol s.J., Gukovskaya a.s. organelly disfunkcii v patogeneze pankreatita. antioksid. [organellar dysfunction in the pathogenesis of pancreatitis. Antioxid]. Redox Signal., 2011; 15(10): 2699-2710.
  23. Gupta s. Faktor-Al'fa-inducirovannogo nekroza opuholi apoptoz T-kletok ot vozrasta cheloveka: rol' TNFr-I i nizhelezhashchih signal'nyh molekul. [Tumor necrosis factor-alpha-induced apoptosis in T cells from aged humans: a role of TNFr-i and downstream signaling molecules]. Exp. Gerontol., 2002; 37(2-3): 93-99.
  24. hashimoto D., ohmuraya M., hirota M. et al. uchastie autofagii v aktivacii tripsinogena v podzheludochnoj acinusa kletki. [involvement of autophagy in trypsinogen activation within the pancreatic acinar cells]. J. Cell Biol., 2008; 181 (7): 1065-1072.
  25. he s., Wang L., Miao L. et al. vzaimodejstvie receptornogo belka kinazy-3 opredelyaet nekroticheskie reakcii kletochnogo TNFalpha. [receptor interacting protein kinase-3 determines cellular necrotic response to TNFalpha]. Cell, 2009; 137(6): 1100-1111.
  26. henriquez M., armisén r., stutzin a., Quest a.F. Gibel' kletok putem nekroza, reguliruemoj put'. [Cell death by necrosis, a regulated way to go]. Curr. Mol. Med., 2008; 8(3): 187-206.
  27. ishidoh k., kominami E. Obrabotka i aktivaciya lizosomal'nyh proteinaz. [Processing and activation of lysosomal proteinases]. Biol. Chem., 2002; 383(12): 18271831.
  28. izyumov D.s., avetisyan a.V., Pletjushkina o.Y. et al. «Plata za strah»: tranzitornaya trekhkratnoe snizhenie vnutrikletochnogo aTP urovnya nakladyvaet apoptoza. [«Wages of fear»: transient threefold decrease in intracellular aTPlevel imposes apoptosis]. Biochim. Biophys. Acta., 2004; 1658(1-2): 141-147.
  29. kaiser a.M., saluja a.k., sengupta a. et al. vzaimosvyaz' mezhdu tyazhest'yu, nekroza i apoptoza v pyati modelyah ehksperimental'nogo ostrogo pankreatita. [relationship between severity, necrosis, and apoptosis in five models of experimental acute pancreatitis]. Am. J. Physiol., 1995; 269(5 Pt 1): 1295-1304.
  30. kroemer G., Marino G., Levine B. autofagiya i kompleksnaya reakciya na stress. [autophagy and the integrated stress response]. Mol. Cell., 2010; 40(2): 280-293.
  31. Li P., Nijhawan D., Budihardjo i. et al. Citohroma S i daTP-zavisimogo formirovaniya apaf-1/kaspaza-9 kompleks iniciiruet apoptoticheskoj proteazy kaskada. [Cytochrome c and daTP-dependent formation of apaf-1/caspase-9 complex initiates an apoptotic protease cascade]. Cell, 1997; 91(4): 479-489.
  32. Lü C.X., Fan T.J., hu G.B., Cong r.s. apoptoz-induciruyushchih faktorov i apoptoza. [apoptosis-inducing factor and apoptosis]. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai), 2003; 35(10): 881-885.
  33. Mahajan U.M., Gupta C., Wagh P.r. et al. izmeneniya pri vospalitel'nyh/apoptoznogo puti i modifikacii gistonov na "nordihydroguaiaretic" kislota predotvrashchaet ostrogo pankreatita v shvejcarskih belyh besporodnyh myshej. [alteration in inflammatory/apoptotic pathway and histone modifications by nordihydroguaiaretic acid prevents acute pancreatitis in swiss albino mice]. Apoptosis, 2011; 16(11):1138-1149. 33. Maiuri M.C., Zalckvar E., kimchi a., kroemer G. selfeating and self-killing: crosstalk between autophagy and apoptosis. Nat. Rev. Mol. Cell Biol., 2007; 8(9): 741-752.
  34. Mareninova o.a., hermann k., French s.W. et al. narusheniya autofagii potok posrednichaet acinarnoj obrazovanie vakuolej kletok i aktivaciya tripsinogena v modelyah gryzunov ostrogo pankreatita. [impaired autophagic flux mediates acinar cell vacuole formation and trypsinogen activation in rodent models of acute pancreatitis]. J. Clin. Invest., 2009; 119(11): 3340–3355.
  35. Mareninova o.a., sung k.F., hong P. et al. Gibel' kletok pri pankreatite: kaspaz zashchity ot pankreonekroza. [Cell death in pancreatitis: caspases protect from necrotizing pancreatitis]. J. Biol. Chem., 2006; 281(6): 3370-3381.
  36. Mizuno T., Zhong X., rothstein T.L. FAS-oposredovannyj apoptoz v kletkah B. [Fas-induced apoptosis in B cells]. Apoptosis, 2003; 8(5): 451-460.
  37. Mizushima N., Levine B., Cuervo a.M., klionsky D.J. autofagiya boretsya s bolezn'yu posredstvom sotovoj svyazi samoperevarivaniya.[autophagy fights disease through cellular self-digestion]. Nature, 2008; 451: 1069–1075.
  38. Moquin D., Chan F.k. Molekulyarnaya regulyaciya zaprogrammirovannoj nekroticheskie povrezhdeniya kletok. [The molecular regulation of programmed necrotic cell injury]. Trends Biochem Sci., 2010; 35(8): 434-441.
  39. Moretti L., Cha Y.i., Niermann k.J., Lu B. pereklyuchenie mezhdu apoptoza i autofagii: radiacionno-inducirovannyh ehndoplazmaticheskij retikulum stress? [switch between apoptosis and autophagy: radiation-induced endoplasmic reticulum stress]? Cell Cycle, 2007; 6(7): 793-798.
  40. Nakamura Y., Do J.h., Yuan J. et al. vospalitel'nyh kletok, reguliruyushchih r53 i kaspazy pri ostrom pankreatite. [inflammatory cells regulate p53 and caspases in acute pancreatitis]. Am. J. Physiol. Gastrointest. Liver Physiol., 2010; 298(1): 92-100.
  41. Niederau C., Grendell J.h. vnutrikletochnye vakuoli pri ehksperimental'nom ostrom pankreatite u krys i myshej podkislennoj otseka. [intracellular vacuoles in experimental acute pancreatitis in rats and mice are an acidified compartment]. J. Clin. Invest., 1988; 81: 229–236.
  42. Nixon r.a., Yang D.s., Lee J.h. Lizosomal'nyh nejrodegenerativnyh rasstrojstv: kontinuum ot razvitiya v pozdnem vozraste.[Neurodegenerative lysosomal disorders: a continuum from development to late age]. Autophagy, 2008; 4(5): 590-599.
  43. orlichenko L., stolz D.B., Noel P. et al. ADF-ribozilirovaniya faktora 1 belok reguliruet aktivaciyu tripsinogena cherez torgovlyu organell iz prokacepsina B belka i sozrevanie autofagii pri ostrom pankreatite. [aDP-ribosylation factor 1 protein regulates trypsinogen activation via organellar trafficking of procathepsin B protein and autophagic maturation in acute pancreatitis]. J. Biol. Chem., 2012; 287 (29): 24284-24293.
  44. Padanilam B.J. Kletochnoj smerti, vyzvannoj ostroj pochechnoj travmatizma: perspektivy na vklad apoptoza i nekroza. [Cell death induced by acute renal injury: a perspective on the contributions of apoptosis and necrosis]. Am. J. Physiol. Renal Physiol., 2003; 284(4): 608-627.
  45. Pandol s.J., Poucell-hatton s. Mekhanizmy kletochnoj gibeli posle zakuporki protoka podzheludochnoj zhelezy v opossumov i krys.[Mechanisms of cell death after pancreatic duct obstruction in the opossum and the rat]. Gastroenterology, 1996; 110(3): 875-884.
  46. rozengurt E. Proteinkinaza d signalizacii: neskol'ko biologicheskih funkcij v norme i patologii. [Protein kinase D signaling: multiple biological functions in health and disease]. Physiology (Bethesda), 2011; 26(1): 23-33.
  47. sandoval D., Gukovskaya a., reavey P. et al. Rol' nejtrofilov i trombocitov aktiviruyushchego faktora, oposredstvuyushchego v ehksperimental'nom pankreatite. [The role of neutrophils and platelet-activating factor in mediating experimental pancreatitis]. Gastroenterology, 1996; 111(4): 1081-1091.
  48. satoh a., Gukovskaya a.s., Nieto J.M. et al. PkC-delta and -epsilon regulate NF-kappaB activation induced by cholecystokinin and TNF-alpha in pancreatic acinar cells. Am. J. Physiol. Gastrointest. Liver Physiol., 2004; 287(3): 582-591.
  49. sung k.F., odinokova i.V., Mareninova o.a. et al. Pro vyzhivanie i bcl-2 belkov stabilizirovat' podzheludochnoj mitohondrii i zashchity ot nekroza pri ehksperimental'nom pankreatite. [Prosurvival Bcl-2 proteins stabilize pancreatic mitochondria and protect against necrosis in experimental pancreatitis]. Exp. Cell Res., 2009; 315(11): 1975-1989.
  50. Thorburn a. Receptor-inducirovannogo smerti, ubivaya kletki. [Death receptor-induced cell killing]. Cell Signal, 2004; 16(2): 139-144.
  51. Thrower E.C., Gorelick F.s., husainb s.Z. Molekulyarnye i kletochnye mekhanizmy travmy podzheludochnoj zhelezy. [Molecular and cellular mechanisms of pancreatic injury]. Curr. Opin. Gastroenterol., 2010; 26(5): 484–489.
  52. Thrower E.C., Yuan J., Usmani a., Liu Y., Jones C., Minervini s.N., alexandre M., Pandol s.J., Guha s. roman proteinkinazy ingibitor d oslablyaet nachale sobytij ehksperimental'nogo pankreatita v izolirovannyh krys acinusov. [a novel protein kinase D inhibitor attenuates early events of experimental pancreatitis in isolated rat acini]. Am. J. Physiol. Gastrointest. Liver Physiol., 2011; 300(1): 120-129.
  53. Vandenabeele P., Declercq W., Van herreweghe F., Vanden Berghe T. Rol' kinaz riP1 i riP3 v FNO-inducirovannogo nekroza. [The role of the kinases riP1 and riP3 in TNFinduced necrosis]. Sci. Signal, 2010; 3(115): 4.
  54. Vanlangenakker N., Vanden Berghe T., krysko D.V. et al. Molekulyarnye mekhanizmy i patofiziologiya nekroticheskoj gibeli kletok. [Molecular mechanisms and pathophysiology of necrotic cell death]. Curr. Mol. Med., 2008; 8(3): 207-220.
  55. Vercammen D., Beyaert r., Denecker G. et al. ingibirovanie kaspaz povyshaet chuvstvitel'nost' L929 kletok k nekrozu, oposredovannyj faktorom nekroza opuholi. [inhibition of caspases increases the sensitivity of L929 cells to necrosis mediated by tumor necrosis factor]. J. Exp. Med., 1998; 187(9): 1477-1485.
  56. Vercammen D., Brouckaert G., Denecker G. et al. Dvojnoj signalizacii receptora FAS: posvyashchenie kak apoptoticheskoj i nekroticheskoj gibeli kletok putej. [Dual signaling of the Fas receptor: initiation of both apoptotic and necrotic cell death pathways]. J. Exp. Med., 1998; 188(5): 919-930.
  57. Voronina s.G., Barrow s.L, simpson a.W. et al. Dinamicheskie izmeneniya v citozol'noj i mitohondrial'noj urovnya ATF v pankreaticheskih acinarnyh kletok. [Dynamic changes in cytosolic and mitochondrial aTP levels in pancreatic acinar cells]. Gastroenterology, 2010; 138(5): 1976-1987.
  58. Wang J., Chen G., Gong h. et al. uluchshenie ehksperimental'nogo ostrogo pankreatita otvarami " Dachengqi "cherez regulirovanie nekroz-apoptoz pereklyuchatel' v pankreaticheskih acinarnyh kletok.[amelioration of experimental acute pancreatitis with Dachengqi Decoction via regulation of necrosis-apoptosis switch in the pancreatic acinar cell]. PLoS One, 2012; 7(7): 40160.
  59. Watanabe o., Baccino F.M., steer M.L., Meldolesi J. supra maksimal'naya stimulyaciya caerulein i ul'trastruktury acinarnyh kletok podzheludochnoj zhelezy krys: rannie morfologicheskie izmeneniya pri razvitii ehksperimental'nogo pankreatita. [supramaximal caerulein stimulation and ultrastructure of rat pancreatic acinar cell: early morphological changes during development of experimental pancreatitis]. Am. J. Physiol., 1984; 246 (4 Pt 1): 457-467.
  60. Weng T.i., Wu h.Y., Chen B.L., Liu s.h. honokiol oslablyaet tyazhest' ostrogo pankreatita i svyazannyh s povrezhdeniem legkih cherez uskorenie acinoznyh kletok apoptoza. [honokiol attenuates the severity of acute pancreatitis and associated lung injury via acceleration of acinar cell apoptosis]. Shock,. 2012; 37(5): 478-484.
  61. Xie Z., klionsky D.J. formirovanie autofagosomii: osnovnye mashiny i prisposobleniya. [autophagosome formation: core machinery and adaptations]. Nat. Cell Biol., 2007; 9(10): 1102-1109.
  62. Yuan J., Liu Y., Tan T. et al. Proteinkinaza D reguliruet putej smerti kletki v ehksperimental'nom pankreatite. [Protein kinase d regulates cell death pathways in experimental pancreatitis]. Front Physiol.,. 2012; 3: 60.
  63. Zhang D.W., shao J., Lin J. et al. riP3, ehnergeticheskij metabolizm regulyator, kotoryj pereklyuchaet FNO-inducirovannaya gibel' kletok ot apoptoza k nekrozu. [riP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis]. Science, 2009; 325(5938): 332336. recieved 16.10.2012

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