Autophagy in Pancreatic Acinar Cells in Caerulein-treated Mice:Immunolocalization of Related Proteins and Their Potential as Markers of Pancreatitis

Toxicologic Pathology

Volumn 42, Issue 2, 2014, Pages 435-457

  Zhang, Leshuai ^a   Zhang, Jun ^a   Shea, Katherine ^a   xu, Lin ^a   Tobin, Grainne ^a   Knapton, Alan ^a   Sharron, Stewart ^a   Rouse, Rodney ^a  

^a CENTER FOR DRUG EVALUATION AND RESEARCH   (United States)

Author keywords

apoptosis; autophagosome; lysosome; necrosis; trypsinogen activation

Indexed keywords

ANTIBODY; BECLIN 1; CATHEPSIN B; CATHEPSIN D; CELL PROTEIN; CERULETIDE; LYSOSOME ASSOCIATED MEMBRANE PROTEIN 2; MICROTUBULE ASSOCIATED PROTEIN 1; PANCREATIC ACUTE RESPONSE PROTEIN; TRIACYLGLYCEROL LIPASE; UNCLASSIFIED DRUG; VACUOLE MEMBRANE PROTEIN 1;

ACINAR CELL; AMYLASE BLOOD LEVEL; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; AUTOLYSOSOME; AUTOPHAGOSOME; AUTOPHAGY; CELL VACUOLE; CONTROLLED STUDY; CYTOPLASM; DISEASE MARKER; EXPERIMENTAL PANCREATITIS; IMMUNOLOCALIZATION; LIGHT CHAIN; MOUSE; NONHUMAN; PRIORITY JOURNAL;

APOPTOSIS; AUTOPHAGOSOME; LYSOSOME; NECROSIS; TRYPSINOGEN ACTIVATION.;

ACINAR CELLS; AMYLASES; ANIMALS; AUTOPHAGY; BIOLOGICAL MARKERS; CERULETIDE; IMMUNOHISTOCHEMISTRY; LIPASE; MALE; MICE; MICE, INBRED C57BL; NECROSIS; PANCREAS; PANCREATITIS; PROTEINS;

EID: 84893519731     PISSN: 01926233     EISSN: 15331601     Source Type: Journal    
DOI: 10.1177/0192623313486967     Document Type: Article

References (91)

1. Adler G. Hahn C. Kern H. F. Rao K. N. (1985). Cerulein-induced pancreatitis in rats: Increased lysosomal enzyme activity and autophagocytosis. Digestion 32, 10–18.
2. Adler G. Rohr G. Kern H. F. (1982). Alteration of membrane fusion as a cause of acute pancreatitis in the rat. Dig Dis Sci 27, 993–1002.
3. Andersen V. Sonne J. Andersen M. (2001). Spontaneous reports on drug-induced pancreatitis in Denmark from 1968 to 1999. Eur J Clin Pharmacol 57, 517–21.
4. Badalov N. Baradarian R. Iswara K. Li J. Steinberg W. Tenner S. (2007). Drug-induced acute pancreatitis: An evidence-based review. Clin Gastroenterol Hepatol 5, 648–61.
5. Balani A. R. Grendell J. H. (2008). Drug-induced pancreatitis: Incidence, managment and prevention. Drug Saf 31, 823–37.
6. Baskin-Bey E. Canbay A. Bronk S. Werneburg N. Guicciardi M. Nyberg S. Gores G. (2005). Cathepsin B inactivation attenuates hepatocyte apoptosis and liver damage in steatotic livers after cold ischemia-warm reperfusion injury. Am J Gastrointest Liver Physiol 288, G396–402.
7. Beaudoin A. R. Grondin G. Lord A. Roberge M. St-Jean P. (1983). The origin of the zymogen granule membrane of the pancreatic acinar cell as examined by ultrastructural cytochemistry of acid phosphatase, thiamine pyrophosphatase, and ATP-diphosphohydrolase activities. Eur J Cell Biol 29, 218–25.
8. Bhatia M. Neoptolemos J. P. Slavin J. (2001). Inflammatory mediators as therapeutic targets in acute pancreatitis. Curr Opin Investig Drugs 2, 496–501.
9. Bhoopathi P. Chetty C. Gujrati M. Dinh D. Rao J. Lakka S. (2010). Cathepsin B facilitates autophagy-mediated apoptosis in SPARC overexpressed primitive neuroectodermal tumor cells. Cell Death Different 17, 1529–39.
10. Bidere N. Lorezo H. Carmona S. Laforge M. Harper F. Dumont C. Senik A. (2003). Cathepsin D triggers bax activation, resulting in selective apoptosis-inducing factor (AIF) relocation in T lymphocytes entering the early commitment phase to apoptosis. J Biol Chem 278, 31401–11.
11. Bursch W. Hochegger K. Torok L. Marian B. Ellinger A. Hermann R. S. (2000). Autophagic and apoptotic types of programmed cell death exhibit different fates of cytoskeletal filaments. J Cell Sci 113, 1189–98.
12. Carew J. Espitia C. Esquivel J. II Mahalingam D. Kelly K. Reddy G. Giles F. Nawrocki S. (2010). Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem 286, 6602–13.
13. Cash H. L. Whitham C. V. Behrendt C. L. Hooper L. V. (2006). Symbiotic bacteria direct expression of an intestinal bactericidal lectin. Science 313, 1126–30.
14. Castino R. Davies J. Beaucourt S. Isidoro C. Murphy D. (2005). Autophagy is a prosurvival mechanism in cells expressing an autosomal dominant familial neurohypophyseal diabetes insipidus mutant vasopressin transgene. FASEB J 19, 1021–23.
15. Cavard C. Terris B. Grimber G. Christa L. Audard V. Radenen-Bussiere B. Simon M. T. Renard C. A. Buendia M. A. Perret C. (2006). Overexpression of regenerating islet-derived 1 alpha and 3 alpha genes in human primary liver tumors with beta-catenin mutations. Oncogene 25, 599–608.
16. Chan E. Y. (2012). Regulation and function of uncoordinated-51 like kinase proteins. Antioxid Redox Signal 17, 775–85.
17. Conus S. Perozzo R. Reinheckel T. Peters C. Scapozza L. Yousefi S. Simon H. (2008). Caspase-8 is activated by cathepsin D initiating neutrophil apoptosis during the resolution of inflammation. J Exp Med 205, 685–98.
18. De León D. D. Farzad C. Crutchlow M. F. Brestelli J. Tobias J. Kaestner K. H. Stoffers D. A. (2006). Identification of transcriptional targets during pancreatic growth after partial pancreatectomy and exendin-4 treatment. Physiol Genomics 24, 133–43.
19. Denker P. S. Dimarco P. E. (2006). Exenatide (exendin-4)-induced pancreatitis: A case report. Diabetes Care 29, 471.
20. Devanath A. Kumari J. Joe J. Peter S. Rajan S. Sabu L. Shivshankar Mary, J. Smitha Roselin, and Arokiasami. (2009). Usefulness of lipase/amylase ratio in acute pancreatitis in South Indian population. Indian J Clin Biochem 24, 361–65.
21. Eskelinen E. L. (2006). Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy. Mol Aspects Med 27, 495–502.
22. Fish J. E. Matouk C. C. Yeboah E. Bevan S. C. Khan M. Patil K. Ohh M. Marsden P. A. (2007). Hypoxia-inducible expression of a natural cis-antisense transcript inhibits endothelial nitric-oxide synthase. J Biol Chem 282, 15652–66.
23. Fortunato F. Bürgers H. Bergmann F. Rieger P. Büchler M. W. Kroemer G. Werner J. (2009). Impaired autolysosome formation correlates with Lamp-2 depletion: Role of apoptosis, autophagy, and necrosis in pancreatitis. Gastroenterology 137, 350–60.
24. Fortunato F. Kroemer G. (2009). Impaired autophagosome-lysosome fusion in the pathogenesis of pancreatitis. Autophagy 5, 850–53.
25. Ge J. Zhao G. Chen R. Li S. Wang S. Zhang X. Zhuang Y. Du J. Yu X. Li G. Yang Y. (2006). Enhanced myocardial cathelpsin B expression inpatients with dilated cardiomyopathy. Europ J Heart Fail 8, 284–89.
26. Gironella M. Folch-Puy E. LeGoffic A. Garcia S. Christa L. Smith A. Tebar L. Hunt S. P. Bayne R. Smith A. J. Dagorn J. C. Closa D. Iovanna J. L. (2007). Experimental acute pancreatitis in PAP/HIP knock-out mice. Gut 56, 1091–97.
27. Gonzalez-Polo R. Boya P. Pauleau A. Jalil A. Larochette N. Souquere S. Eskelinen E. Pierron G. Saftiz P. Kroemer G. (2005). The apoptosis/autophagy paradox: Autophagic vacuolization before apoptotic death. J Cell Scien 118, 3091–102.
28. Grasso D. Ropolo A. Lo Ré A. Boggio V. Molejón M. I. Iovanna J. L. Gonzalez C. D. Urrutia R. Vaccaro M. I. (2011). Zymophagy, a novel selective autophagy pathway mediated by VMP1-USP9x-p62, prevents pancreatic cell death. J Biol Chem 286, 8308–24.
29. Greenbaum L. M. Hirshkowitz A. Shoichet I. (1959). The activation of trypsinogen by cathepsin B. J Biol Chem 234, 2885–90.
30. Hah Y. Noh H. Ha J. Ahn J. Hahm J. Cho H. Kim D. (2012). Cathepsin D inhibits oxidative stress-induced cell death via activation of autophagy in cancer cells. J Can Let 323, 208–14.
31. Halangk W. Lerch M. M. Brandt-Nedelev B. Roth W. Ruthenbuerger M. Reinheckel T. Domschke W. Lippert H. Peters C. Deussing J. (2000). Role of cathepsin B in intracellular trypsinogen activation and the onset of acute pancreatitis. J Clin Invest 106, 773–81.
32. Hamagami K. Sakurai Y. Shintani N. Higuchi N. Ikeda K. Hashimoto H. Suzuki A. Kiyama H. Baba A. (2009). Over-expression of pancreatic pituitary adenylate cyclase-activating polypeptide (PACAP) aggravates cerulein-induced acute pancreatitis in mice. J Pharmacol Sci 110, 451–58.
33. Hamasaki M. Yoshimori T. (2010). Where do they come from? Insights into autophagosome formation. FEBS Lett 584, 1296–301.
34. Hashimoto D. Ohmuraya M. Hirota M. Yamamoto A. Suyama K. Ida S. Okumura Y. Takahashi E. Kido H. Araki K. Baba H. Mizushima N. Yamamura K. (2008). Involvement of autophagy in trypsinogen activation within the pancreatic acinar cells. J Cell Biol 181, 1065–72.
35. Hofbauer B. Saluja A. K. Lerch M. M. Bhagat L. Bhatia M. Lee H. S. Frossard J. L. Adler G. Steer M. L. (1998). Intra-acinar cell activation of trypsinogen during caerulein-induced pancreatitis in rats. Am J Physiol 275, G352–62.
36. Horie A. Takino T. Herman L. Fitzgerald P. J. (1971). Pancreas acinar cell regeneration. 8. Relationship of acid phosphatase and beta-glucuronidase to intracellular organelles and ethionine lesions. Am J Pathol 63, 299–318.
37. Iovanna J. Orelle B. Keim V. Dagorn J. C. (1991). Messenger RNA sequence and expression of rat pancreatitis-associated protein, a lectin-related protein overexpressed during acute experimental pancreatitis. J Biol Chem 266, 24664–69.
38. Itakura E. Mizushima N. (2010). Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins. Autophagy 6, 764–76.
39. Jang Y. Thorn P. (2011). Visualization of exocytosis in pancreatic acinar cells by fluorescence microscopy. The Pancreapedia: Exocrine Pancreas Knowledge Base, www.pancreapedia.org.tools/methods. doi:10.3998/panc.2011.15
40. Jiang P. H. Motoo Y. Vaccaro M. I. Iovanna J. L. Okada G. Sawabu N. (2004). Expression of vacuole membrane protein 1 (VMP1) in spontaneous chronic pancreatitis in the WBN/Kob rat. Pancreas 29, 225–30.
41. Jing D. Kehoe D. E. Tzanakakis E. S. (2010). Expression of Reg family proteins in embryonic stem cells and its modulation by Wnt/beta-catenin signaling. Stem Cells Dev 19, 1307–19.
42. Kabeya Y. Mizushima N. Ueno T. Yamamoto A. Kirisako T. Noda T. Kominami E. Ohsumi Y. Yoshimori T. (2000). LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19, 5720–28.
43. Kanthasamy A. Anantharam V. Ali S. F. Kanthasamy A. G. (2006). Methamphetamine induces autophagy and apoptosis in a mesencephalic dopaminergic neuronal culture model: Role of cathepsin-D in methamphetamine-induced apoptotic cell death. Ann N Y Acad Sci 1074, 234–44.
44. Kern H. F. Adler G. Scheele G. A. (1985). Structural and biochemical characterization of maximal and supermaximal hormonal stimulation of rat exocrine pancreas. Scand J Gastroenterol 20, 20–29.
45. Lancashire R. J. Cheng K. Langman M. J. (2003). Discrepancies between population-based data and adverse reaction reports in assessing drugs as causes of acute pancreatitis. Aliment Pharmacol Ther 17, 887–93.
46. Lyer S. N. Drake A. J. 3rd West R. L. Mendez C. E. Tanenberg R. J. (2012). Case report of acute necrotizing pancreatitis associated with combination treatment of sitagliptin and exenatide. Endocr Pract 18, e10–13.
47. Maiuri M. Zalckvar E. Kimchi A. Kroemer G. (2007). Self-eating and self-killing: Crosstalk between autophagy and apoptosis. Nature Rev 8, 741–52.
48. Mansfield C. (2012). Pathophysiology of acute pancreatitis: Potential application from experimental models and human medicine to dogs. J Vet Intern Med 26, 875–87.
49. Means A. L. Meszoely I. M. Suzuki K. Miyamoto Y. Rustgi A. K. Coffey R. J. Jr Wright C. V. Stoffers D. A. Leach S. D. (2005). Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediates. Development 132, 3767–76.
50. Mizushima N. Levine B. Cuervo A. Klionsky D. (2008). Autophagy fights disease through cellular self-digestion. Nature 451, 1069–75.
51. Mizushima N. Yoshimori T. Levine B. (2010). Methods in mammalian autophagy research. Cell 140, 313–26.
52. Nakatogawa H. Suzuki K. Kamada Y. Ohsumi Y. (2009). Dynamics and diversity in autophagy mechanisms: Lessons from yeast. Nature Rev 10, 458–67.
53. Narushima Y. Unno M. Nakagawara K. Mori M. Miyashita H. Suzuki Y. Noguchi N. Takasawa S. Kumagai T. Yonekura H. Okamoto H. (1997). Structure, chromosomal localization and expression of mouse genes encoding type III Reg, RegIII alpha, RegIII beta, RegIII gamma. Gene 185, 159–68.
54. Niederau C. Ferrell L. D. Grendell J. H. (1985). Caerulein-induced acute necrotizing pancreatitis in mice: Protective effects of proglumide, benzotript, and secretin. Gastroenterology 88, 1192–204.
55. Niederau C. Grendell J. H. (1988). Intracellular vacuoles in experimental acute pancreatitis in rats and mice are an acidified compartment. J Clin Invest 81, 229–36.
56. Norkina O. Graf R. Appenzeller P. De Lesie R. C. (2006). Caerulein-induced acute pancreatitis in mice that constitutively overexpress Reg/PAP genes. BMC Gastroenterology 6, 16.
57. Ortiz E. M. Dusetti N. J. Vasseur S. Malka D. Bödeker H. Dagorn J. C. Iovanna J. L. (1998). The pancreatitis-associated protein is induced by free radicals in AR4-2J cells and confers cell resistance to apoptosis. Gastroenterology 114, 808–16.
58. Ohmuraya M. Yamamura K. (2008). Autophagy and acute pancreatitis: A novel autophagy theory for trypsinogen activation. Autophagy 4, 1060–62.
59. Pardo R. Lo Re A. Archange C. Ropolo A. Papademetrio D. L. Gonzalez C. D. Alvarez E. M. Iovanna J. L. Vaccaro M. I. (2010). Gemcitabine induces the VMP1-mediated autophagy pathway to promote apoptotic death in human pancreatic cancer cells. Pancreatology 10, 19–26.
60. Rao K. N. Furetti M. F. Baccino F. M. (1980). Acute hemorrhagic pancreatic necrosis in mice. The activity of lysosomal enzymes in the pancreas and the liver. Am J Pathol 98, 45–60.
61. Rattner D. (1996). Experimental models of acute pancreatitis and their relevance to human disease. Scand J Gastroenterol Suppl 219, 6–9.
62. Reggiori F. Monastyrska I. Shintani T. Klionsky D. J. (2005). The actin cytoskeleton is required for selective types of autophagy, but not nonspecific autophagy, in the yeast Saccharomyces cerevisiae. Mol Biol Cell 16, 5843–56.
63. Repnik U. Stoka V. Turk V. Turk B. (2012). Lysosomes and lysosomal cathepsins in cell death. Biochimica et Biophysica Acta 1824, 22–33.
64. Resau J. H. Marzella L. Jones R. T. Trump B. F. (1985). What’s new in in vitro studies of exocrine pancreatic cells injury? Path Res Pract 179, 576–88.
65. Ropolo A. Grasso D. Pardo R. Sacchetti M. L. Archange C. Lo Re A. Seux M. Nowak J. Gonzalez C. D. Iovanna J. L. Vaccaro M. I. (2007). The pancreatitis-induced vacuole membrane protein 1 triggers autophagy in mammalian cells. J Biol Chem 282, 37124–33.
66. Ryu H. J. Kim J. E. Yeo S. I. Kim D. W. Kwon O. S. Choi S. Y. Kang T. C. (2011). F-actin depolymerization accelerates clasmatodendrosis via activation of lysosome-derived autophagic astroglial death. Brain Res Bull 85, 368–73.
67. Saftig P. Beertsen W. Eskelinen E. L. (2008). LAMP-2: A control step for phagosome and autophagosome maturation. Autophagy 44, 510–12.
68. Sakorafas G. H. Tsiotou A. G. (2000). Etiology and pathogenesis of acute pancreatitis: Current concepts. J Clin Gastroenterol 30, 343–56.
69. Saluja A. Hashimoto S. Saluja M. Powers R. E. Meldolesi J. Steer M. L. (1987). Subcellular redistribution of lysosomal enzymes during caerulein-induced pancreatitis. Am J Physiol 253, G508–16.
70. Saluja A. Saito I. Saluja M. Houlihan M. J. Powers R. E. Meldolesi J. Steer M. (1985). In vivo rat pancreatic acinar cell function during supramaximal stimulation with caerulein. Am J Physiol 249, G702–10.
71. Salvesen G. (2001). A lysosomal protease enters the death scene. J Clin Invest 107, 21–22.
72. Singh V. McNiven M. (2008). Src-mediated cotractin phosphorylation regulates actin localization and injurious blebbing in acinar cells. Mol Biol Cell 19, 2339–47.
73. Singh V. Saluja A. Bhagat L. Hietaranta A. Song A. Mykoniatis A. Van Acker G. Steer M. (2001). Serine protease inhibitor causes F-actin redistribution and inhibition of calcium-mediated secretion in pancreatic acini. Gastroenterol 120, 1818–27.
74. Steer M. Meldolesi J. Figaralla C. (1984). Pancreatitis. The role of lysosomes. Dig Dis Sci 29, 934–38.
75. Takeshige K. Baba M. Tsuboi S. Noda T. Ohsumi Y. (1992). Autophagy in yeast demonstrated with proteinase-deficient mutants and conditions for its induction. J Cell Biol 119, 301–11.
76. Tamura H. Shibata M. Koike M. Sasaki M. Uchiyama Y. (2010). Atg9A protein, an autophagy-related membrane protein, is localized in the neurons of mouse brains. J Histochem Cytochem 58, 443–53.
77. Tanida I. Minematsu-Ikeguchi N. Ueno T. Kominami E. (2005). Lysosomal turnover, but not a cellular level, of endogenous LC3 is a marker for autophagy. Autophagy 1, 84–91.
78. Thorburn A. (2008). Apoptosis and autophagy: Regulatory connections between two supposedly different processes. Apoptosis 13, 1–9.
79. Trivedi C. D. Pitchumoni C. S. (2005). Drug-induced pancreatitis: An update. J Clin Gastroenterol 39, 709–16.
80. Uchiyama Y. (2001). Autophagic cell death and its execution by lysosomal cathepsins. Arch Histol Cytol 64, 233–46.
81. Underwood T. W. Frye C. B. (1993). Drug-induced pancreatitis. Clin Pharm 6, 440–48.
82. Vaccaro M. I. Ropolo A. Grasso D. Iovanna J. L. (2008). A novel mammalian trans-membrane protein reveals an alternative initiation pathway for autophagy. Autophagy 4, 388–90.
83. Wang Y. Jacovetti C. Li B. Siddique T. Xiong X. Yin H. Wang M. Zhao H. Liu J. L. (2011). Coordinated age-dependent and pancreatic-specific expression of mouse Reg2Reg3a, and Reg3b genes. Growth Factors 29, 72–81.
84. Watanabe O. Baccino F. M. Steer M. L. Meldolesi J. (1984). Supramaximal caerulein stimulation and ultrastructure of rat pancreatic acinar cell: Early morphological changes during development of experimental pancreatitis. Am J Physiol 246, G457–67.
85. Willemer S. Bialek R. Adler G. (1990). Localization of lysosomal and digestive enzymes in cytoplasmic vacuoles in caerulein-pancreatitis. Histochemistry 94, 161–70.
86. Xie Z. Klionsky D. (2007). Autophagosome formation: Core machinery and adaptations. Nature Cell 9, 1102–9.
87. Yamada T. Carson A. R. Caniggia I. Umebayashi K. Yoshimori T. Nakabayashi K. Scherer S. W. (2005). Endothelial nitric-oxide synthase antisense (NOS3AS) gene encodes an autophagy-related protein (APG9-like2) highly expressed in trophoblast. J Biol Chem 280, 18283–90.
88. Yilmaz U. E. Yilmaz N. Titiz I. Basaranoglu M. Tarcin O. (2012). The utility of amylase and lipase as reliable predictive markers for functioning renal graft. Ann Transplant 17, 77–84.
89. Young A. R. Chan E. Y. Hu X. W. Köchl R. Crawshaw S. G. High S. Hailey D. W. Lippincott-Schwartz J. Tooze S. A. (2006). Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes. J Cell Sci 119, 3888–900.
90. Zeng X. Overmeyer J. H. Maltese W. A. (2006). Functional specificity of the mammalian Beclin-Vps34 PI 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking. J Cell Sci 119, 259–70.
91. Zhang J. Goering P. Espandiari P. Shaw M. Bonventre J. Vaidya V. S. Brown R. P. Keenan J. Kilty C. Sadrieh N. Hanig J. P. (2009). Differences in immunolocalization of Kim-1, RPA-1, and RPA-2 in kidneys of gentamicin-, cisplatin-, and valproic acid-treated rats: Potential role of iNOS and nitrotyrosine. Toxicol Pathol 37, 629–43.