General control nonderepressible 2 deletion predisposes to asparaginase-associated pancreatitis in mice

American Journal of Physiology - Gastrointestinal and Liver Physiology

Volumn 310, Issue 11, 2016, Pages G1061-G1070

  Phillipson Weiner, Lindsey ^a   Mirek, Emily T ^a   Wang, Yongping ^a   McAuliffe, W Geoffrey ^d   Wek, Ronald C ^e   Anthony, Tracy G ^a,b,c  

^a RUTGERS UNIVERSITY   (United States)

^b RUTGERS CANCER INSTITUTE OF NEW JERSEY   (United States)

^c State University of New Jersey   (United States)

^d ROBERT WOOD JOHNSON MEDICAL SCHOOL   (United States)

^e INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Amino acid response; Endoplasmic reticulum stress; Eukaryotic initiation factor 2; Protein kinase R like ER kinase; Unfolded protein response

Indexed keywords

ACTIVATING TRANSCRIPTION FACTOR 3; ACTIVATING TRANSCRIPTION FACTOR 4; ACTIVATING TRANSCRIPTION FACTOR 6; ASPARAGINASE; FIBROBLAST GROWTH FACTOR 21; GENERAL CONTROL NONDEREPRESSIBLE 2 PROTEIN; HEAT SHOCK PROTEIN 70; INITIATION FACTOR 2; MESSENGER RNA; PANCREATITIS ASSOCIATED PROTEIN; PROTEIN KINASE R; PROTEIN KINASE R LIKE ER KINASE; SIRTUIN 1; TUMOR NECROSIS FACTOR; UNCLASSIFIED DRUG; X BOX BINDING PROTEIN 1; ZYMOGEN GRANULE; EIF2AK4 PROTEIN, MOUSE; FIBROBLAST GROWTH FACTOR; HEAT SHOCK PROTEIN; MOLECULAR CHAPERONE GRP78; PERK KINASE; PROTEIN SERINE THREONINE KINASE; SIRT1 PROTEIN, MOUSE; TRANSCRIPTION FACTOR; TRIACYLGLYCEROL; XBP1 PROTEIN, MOUSE;

ACINAR CELL; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL SWELLING; CELL VACUOLE; CONTROLLED STUDY; ENDOPLASMIC RETICULUM; ENDOPLASMIC RETICULUM STRESS; ENZYME PHOSPHORYLATION; EXOCRINE PANCREAS; EXPERIMENTAL PANCREATITIS; FEMALE; GENE DELETION; GENE TARGETING; GENETIC PREDISPOSITION; MALE; MOUSE; NONHUMAN; ORGAN WEIGHT; OXIDATIVE STRESS; PRIORITY JOURNAL; TISSUE SECTION; TRANSMISSION ELECTRON MICROSCOPY; WILD TYPE; ANIMAL; AUTOPHAGY; C57BL MOUSE; CYTOLOGY; DRUG EFFECTS; GENETICS; METABOLISM; PANCREAS; PANCREATITIS; PATHOLOGY;

ACINAR CELLS; ANIMALS; ASPARAGINASE; AUTOPHAGY; EIF-2 KINASE; ENDOPLASMIC RETICULUM STRESS; FEMALE; FIBROBLAST GROWTH FACTORS; GENE DELETION; HEAT-SHOCK PROTEINS; MALE; MICE; MICE, INBRED C57BL; PANCREAS; PANCREATITIS; PROTEIN-SERINE-THREONINE KINASES; SIRTUIN 1; TRANSCRIPTION FACTORS; TRIGLYCERIDES; TUMOR NECROSIS FACTOR-ALPHA; X-BOX BINDING PROTEIN 1;

EID: 84984629302     PISSN: 01931857     EISSN: 15221547     Source Type: Journal    
DOI: 10.1152/ajpgi.00052.2016     Document Type: Article

References (67)

1. Aldoss I, Douer D, Behrendt CE, Chaudhary P, Mohrbacher A, Vrona J, Pullarkat V. Toxicity profile of repeated doses of PEG-asparaginase incorporated into a pediatric-type regimen for adult acute lymphoblastic leukemia. Eur J Haematol 96: 375–380, 2016.
2. Alvarez OA, Zimmerman G. Pegaspargase-induced pancreatitis. Med Pediatr Oncol 34: 200–205, 2000.
3. Anthony TG, McDaniel BJ, Byerley RL, McGrath BC, Cavener DR, McNurlan MA, Wek RC. Preservation of liver protein synthesis during dietary leucine deprivation occurs at the expense of skeletal muscle mass in mice deleted for eIF2 kinase GCN 2. J Biol Chem 279: 36553–36561, 2004.
4. Balasubramanian MN, Butterworth EA, Kilberg MS. Asparagine synthetase: regulation by cell stress and involvement in tumor biology. Am J Physiol Endocrinol Metab 304: E789–E799, 2013.
5. Banerji J. Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons. Int J Mol Med 36: 607–626, 2015.
6. Ben Tanfous M, Sharif-Askari B, Ceppi F, Laaribi H, Gagne V, Rousseau J, Labuda M, Silverman LB, Sallan SE, Neuberg D, Kutok JL, Sinnett D, Laverdiere C, Krajinovic M. Polymorphisms of asparaginase pathway and asparaginase-related complications in children with acute lymphoblastic leukemia. Clin Cancer Res 21: 329–334, 2015.
7. Bhatia M. Apoptosis versus necrosis in acute pancreatitis. Am J Physiol Gastrointest Liver Physiol 286: G189–G196, 2004.
8. Bunpo P, Cundiff JK, Reinert RB, Wek RC, Aldrich CJ, Anthony TG. The eIF2 kinase GCN2 is essential for the murine immune system to adapt to amino acid deprivation by asparaginase. J Nutr 140: 2020–2027, 2010.
9. Bunpo P, Dudley A, Cundiff JK, Cavener DR, Wek RC, Anthony TG. GCN2 protein kinase is required to activate amino acid deprivation responses in mice treated with the anti-cancer agent L-asparaginase. J Biol Chem 284: 32742–32749, 2009.
10. Cairo MS. Adverse reactions of L-asparaginase. Am J Pediatr Hematol Oncol 4: 335–339, 1982.
11. Dores GM, Devesa SS, Curtis RE, Linet MS, Morton LM. Acute leukemia incidence and patient survival among children and adults in the United States, 2001–2007. Blood 119: 34–43, 2012.
12. Drago A, Giegling I, Schäfer M, Hartmann AM, Konte B, Friedl M, Serretti A, Rujescu D. Genome-wide association study supports the role of the immunological system and of the neurodevelopmental processes in response to haloperidol treatment. Pharmacogenet Genomics 24: 314–319, 2014.
13. Earl M. Incidence and management of asparaginase-associated adverse events in patients with acute lymphoblastic leukemia. Clin Adv Hematol Oncol 7: 600–606, 2009.
14. El-Nagga NEA, El-Ewasy SM, El-Shweihy NM. Microbial L-asparaginase as a potential therapeutic agent for the treatment of acute lymphoblastic leukemia: the pros and cons. Int J Pharmacol 10: 182–199, 2014.
15. Eyries M, Montani D, Girerd B, Perret C, Leroy A, Lonjou C, Chelghoum N, Coulet F, Bonnet D, Dorfmüller P, Fadel E, Sitbon O, Simonneau G, Tregouët DA, Humbert M, Soubrier F. EIF2AK4 mutations cause pulmonary veno-occlusive disease, a recessive form of pulmonary hypertension. Nat Genet 46: 65–69, 2014.
16. Figueiredo L, Cole PD, Drachtman RA. Asparaginase Erwinia chrysanthemi as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia who have developed hypersensitivity to E. coli-derived asparaginase. Expert Rev Hematol 9: 227–234, 2016.
17. Gukovskaya AS, Gukovsky I. Autophagy and pancreatitis. Am J Physiol Gastrointest Liver Physiol 303: G993–G1003, 2012.
18. Gukovsky I, Pandol SJ, Mareninova OA, Shalbueva N, Jia W, Gukovskaya AS. Impaired autophagy and organellar dysfunction in pancreatitis. J Gastroenterol Hepatol 27 Suppl 2: 27–32, 2012.
19. Hamanaka RB, Bennett BS, Cullinan SB, Diehl JA. PERK and GCN2 contribute to eIF2α phosphorylation and cell cycle arrest after activation of the unfolded protein response pathway. Mol Biol Cell 16: 5493–5501, 2005.
20. Harding HP, Zhang Y, Zeng H, Novoa I, Lu PD, Calfon M, Sadri N, Yun C, Popko B, Paules R, Stojdl DF, Bell JC, Hettmann T, Leiden JM, Ron D. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol Cell 11: 619–633, 2003.
21. Hernandez-Espinosa D, Minano A, Martinez C, Perez-Ceballos E, Heras I, Fuster JL, Vicente V, Corral J. L-Asparaginase-induced antithrombin type I deficiency: implications for conformational diseases. Am J Pathol 169: 142–153, 2006.
22. Hijiya N, van der Sluis IM. Asparaginase-associated toxicity in children with acute lymphoblastic leukemia. Leuk Lymphoma 57: 1–10, 2015.
23. Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med 373: 1541–1552, 2015.
24. Huntington JA. Serpin structure, function and dysfunction. J Thromb Haemost 9 Suppl 1: 26–34, 2011.
25. Hyun JJ, Lee HS. Experimental models of pancreatitis. Clin Endosc 47: 212–216, 2014.
26. Iida K, Li Y, McGrath BC, Frank A, Cavener DR. PERK eIF2α kinase is required to regulate the viability of the exocrine pancreas in mice. BMC Cell Biol 8: 38, 2007.
27. Ji B, Chen X, Misek D, Kuick R, Hanash S, Ernst S, Najarian R, Logsdon C. Pancreatic gene expression during the initiation of acute pancreatitis: identification of EGR-1 as a key regulator. Physiol Genomics 14: 59–72, 2003.
28. Kearney SL, Dahlberg SE, Levy DE, Voss SD, Sallan SE, Silverman LB. Clinical course and outcome in children with acute lymphoblastic leukemia and asparaginase-associated pancreatitis. Pediatr Blood Cancer 53: 162–167, 2009.
29. Kilberg MS, Balasubramanian M, Fu L, Shan J. The transcription factor network associated with the amino acid response in mammalian cells. Adv Nutr 3: 295–306, 2012.
30. Kilberg MS, Shan J, Su N. ATF4-dependent transcription mediates signaling of amino acid limitation. Trends Endocrinol Metab 20: 436–443, 2009.
31. Knoderer HM, Robarge J, Flockhart DA. Predicting asparaginaseassociated pancreatitis. Pediatr Blood Cancer 49: 634–639, 2007.
32. Kroemer G, Marino G, Levine B. Autophagy and the integrated stress response. Mol Cell 40: 280–293, 2010.
33. Kubisch CH, Logsdon CD. Secretagogues differentially activate endoplasmic reticulum stress responses in pancreatic acinar cells. Am J Physiol Gastrointest Liver Physiol 292: G1804–G1812, 2007.
34. Lugea A, Tischler D, Nguyen J, Gong J, Gukovsky I, French SW, Gorelick FS, Pandol SJ. Adaptive unfolded protein response attenuates alcohol-induced pancreatic damage. Gastroenterology 140: 987–997, 2011.
35. Lugea A, Waldron RT, Pandol SJ. Pancreatic adaptive responses in alcohol abuse: role of the unfolded protein response. Pancreatology 15: S1–S5, 2015.
36. Malo A, Kruger B, Goke B, Kubisch CH. 4-Phenylbutyric acid reduces endoplasmic reticulum stress, trypsin activation, and acinar cell apoptosis while increasing secretion in rat pancreatic acini. Pancreas 42: 92–101, 2013.
37. Malo A, Kruger B, Seyhun E, Schafer C, Hoffmann RT, Goke B, Kubisch CH. Tauroursodeoxycholic acid reduces endoplasmic reticulum stress, trypsin activation, and acinar cell apoptosis while increasing secretion in rat pancreatic acini. Am J Physiol Gastrointest Liver Physiol 299: G877–G886, 2010.
38. Mehlem A, Hagberg CE, Muhl L, Eriksson U, Falkevall A. Imaging of neutral lipids by oil red O for analyzing the metabolic status in health and disease. Nat Protoc 8: 1149–1154, 2013.
39. Milman HA, Cooney DA. The distribution of L-asparagine synthetase in the principal organs of several mammalian and avian species. Biochem J 142: 27–35, 1974.
40. Milman HA, Cooney DA, Young DM. Role of pancreatic L-asparagine synthetase in homeostasis of L-asparagine. Am J Physiol Endocrinol Metab Gastrointest Physiol 236: E746–E753, 1979.
41. -induced pancreatitis in children with acute lymphoblastic leukemia: is allopurinol protective? Pediatr Hematol Oncol 27: 496–501, 2010.
42. Pandol SJ, Gorelick FS, Lugea A. Environmental and genetic stressors and the unfolded protein response in exocrine pancreatic function—a hypothesis. Front Physiol 2: 8, 2011.
43. Raja RA, Schmiegelow K, Albertsen BK, Prunsild K, Zeller B, Vaitkeviciene G, Abrahamsson J, Heyman M, Taskinen M, Harila-Saari A, Kanerva J, Frandsen TL. Asparaginase-associated pancreatitis in children with acute lymphoblastic leukaemia in the NOPHO ALL2008 protocol. Br J Haematol 165: 126–133, 2014.
44. Raja RA, Schmiegelow K, Frandsen TL. Asparaginase-associated pancreatitis in children. Br J Haematol 159: 18–27, 2012.
45. Raja RA, Schmiegelow K, Henriksen BM, Leth Frandsen T. Serial ultrasound monitoring for early recognition of asparaginase associated pancreatitis in children with acute lymphoblastic leukemia. Pediatr Hematol Oncol 32: 474–481, 2015.
46. Reinert RB, Oberle LM, Wek SA, Bunpo P, Wang XP, Mileva I, Goodwin LO, Aldrich CJ, Durden DL, McNurlan MA, Wek RC, Anthony TG. Role of glutamine depletion in directing tissue-specific nutrient stress responses to L-asparaginase. J Biol Chem 281: 31222–31233, 2006.
47. Richards NG, Kilberg MS. Asparagine synthetase chemotherapy. Annu Rev Biochem 75: 629–654, 2006.
48. Ron D, Harding HP. Protein-folding homeostasis in the endoplasmic reticulum and nutritional regulation. Cold Spring Harb Perspect Biol 4: a103177, 2012.
49. Rousseau J, Gagne V, Labuda M, Beaubois C, Sinnett D, Laverdiere C, Moghrabi A, Sallan SE, Silverman LB, Neuberg D, Kutok JL, Krajinovic M. ATF5 polymorphisms influence ATF function and response to treatment in children with childhood acute lymphoblastic leukemia. Blood 118: 5883–5890, 2011.
50. Rytting ME. Role of L-asparaginase in acute lymphoblastic leukemia: focus on adult patients. Blood Lymph Cancer Targets Ther 2: 117–124, 2012.
51. Sah RP, Garg SK, Dixit AK, Dudeja V, Dawra RK, Saluja AK. Endoplasmic reticulum stress is chronically activated in chronic pancreatitis. J Biol Chem 289: 27551–27561, 2014.
52. Samarasinghe S, Dhir S, Slack J, Iyer P, Wade R, Clack R, Vora A, Goulden N. Incidence and outcome of pancreatitis in children and young adults with acute lymphoblastic leukaemia treated on a contemporary protocol, UKALL 2003. Br J Haematol 162: 710–713, 2013.
53. Schleis SE, Rizzo SA, Phillips JC, LeBlanc AK. Asparaginase-associated pancreatitis in a dog. Can Vet J 52: 1009–1012, 2011.
54. Seyhun E, Malo A, Schafer C, Moskaluk CA, Hoffmann RT, Goke B, Kubisch CH. Tauroursodeoxycholic acid reduces endoplasmic reticulum stress, acinar cell damage, and systemic inflammation in acute pancreatitis. Am J Physiol Gastrointest Liver Physiol 301: G773–G782, 2011.
55. -dependent regulation of the JMJD3 gene during amino acid deprivation can be rescued in Atf4-deficient cells by inhibition of deacetylation. J Biol Chem 287: 36393–36403, 2012.
56. Shi Y, Vattem KM, Sood R, An J, Liang J, Stramm L, Wek RC. Identification and characterization of pancreatic eukaryotic initiation factor 2 α-subunit kinase, PEK, involved in translational control. Mol Cell Biol 18: 7499–7509, 1998.
57. Siu F, Bain PJ, LeBlanc-Chaffin R, Chen H, Kilberg MS. ATF4 is a mediator of the nutrient-sensing response pathway that activates the human asparagine synthetase gene. J Biol Chem 277: 24120–24127, 2002.
58. Smallwood TL, Small GW, Suter SE, Richards KL. Expression of asparagine synthetase predicts in vitro response to L-asparaginase in canine lymphoid cell lines. Leuk Lymphoma 55: 1357–1365, 2014.
59. Su N, Kilberg MS. C/EBP homology protein (CHOP) interacts with activating transcription factor 4 (ATF4) and negatively regulates the stress-dependent induction of the asparagine synthetase gene. J Biol Chem 283: 35106–35117, 2008.
60. Teske BF, Wek SA, Bunpo P, Cundiff JK, McClintick JN, Anthony TG, Wek RC. The eIF2 kinase PERK and the integrated stress response facilitate activation of ATF6 during endoplasmic reticulum stress. Mol Biol Cell 22: 4390–4405, 2011.
61. Treepongkaruna S, Thongpak N, Pakakasama S, Pienvichit P, Sirachainan N, Hongeng S. Acute pancreatitis in children with acute lymphoblastic leukemia after chemotherapy. J Pediatr Hematol Oncol 31: 812–815, 2009.
62. Vrooman LM, Kirov I, Dreyer ZE, Kelly M, Hijiya N, Brown P, Drachtman RA, Messinger YH, Ritchey AK, Hale GA, Maloney K, Lu Y, Plourde PV, Silverman LB. Activity and toxicity of intravenous Erwinia asparaginase following allergy to E. coli-derived asparaginase in children and adolescents with acute lymphoblastic leukemia. Pediatr Blood Cancer 63: 228–233, 2016.
63. Wang M, Kaufman RJ. Protein misfolding in the endoplasmic reticulum as a conduit to human disease. Nature 529: 326–335, 2016.
64. Wilson GJ, Bunpo P, Cundiff JK, Wek RC, Anthony TG. The eukaryotic initiation factor 2 kinase GCN2 protects against hepatotoxicity during asparaginase treatment. Am J Physiol Endocrinol Metab 305: E1124–E1133, 2013.
65. Wilson GJ, Lennox BA, She P, Mirek ET, Al Baghdadi RJ, Fusakio ME, Dixon JL, Henderson GC, Wek RC, Anthony TG. GCN2 is required to increase fibroblast growth factor 21 and maintain hepatic triglyceride homeostasis during asparaginase treatment. Am J Physiol Endocrinol Metab 308: E283–E293, 2015.
66. Yang F, Chen XD, Tan LJ, Shen J, Li DY, Zhang F, Sha BY, Deng HW. Genome wide association study: searching for genes underlying body mass index in the Chinese. Biomed Environ Sci 27: 360–370, 2014.
67. Zhang P, McGrath BC, Reinert J, Olsen DS, Lei L, Gill S, Wek SA, Vattem KM, Wek RC, Kimball SR, Jefferson LS, Cavener DR. The GCN2 eIF2α kinase is required for adaptation to amino acid deprivation in mice. Mol Cell Biol 22: 6681–6688, 2002.