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Article

Differentially expressed kinase genes associated with trypsinogen activation in rat pancreatic acinar cells treated with taurolithocholic acid 3-sulfate

  • Authors:
    • Biao Ma
    • Lin Wu
    • Ming Lu
    • Bo Gao
    • Xin Qiao
    • Bei Sun
    • Dongbo Xue
    • Weihui Zhang
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Department of Surgery, David Geffen School of Medicine, University of Califonia at Los Angeles, Los Angeles, CA 90095, USA
  • Pages: 1591-1596
    |
    Published online on: March 4, 2013
       https://doi.org/10.3892/mmr.2013.1355
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Abstract

Trypsinogen activation is the initial factor involved in the development of all types of acute pancreatitis (AP) and has been suggested to be regulated by protein kinases. In the present study, AR42J rat pancreatic acinar cells were treated with taurolithocholic acid 3-sulfate (TLC-S), and trypsinogen activation was detected with bis-(CBZ-L-isoleucyl-L-prolyl-L-arginine amide) dihydrochloride (BZiPAR) staining and flow cytometry. Differentially expressed protein kinase genes were screened by Gene Chip analysis, and the functions of these kinases were analyzed. A significantly increased activation of trypsinogen in AR42J cells following treatment with TLC-S was observed. A total of 22 differentially expressed protein kinase genes were found in the TLC-S group, among which 19 genes were upregulated and 3 were downregulated. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, kinase genes of the same KEGG pathways were connected to create a network through signaling pathways, and 10 nodes of kinases were identified, which were mitogen-activated protein kinase (Mapk)8, Mapk14, Map2k4, interleukin-1 receptor-associated kinase 3 (Irak3), ribosomal protein S6 kinase, 90 kDa, polypeptide 2 (Rps6ka2), protein kinase C, alpha (Prkca), v-yes-1 Yamaguchi sarcoma viral related oncogene homolog (Lyn), protein tyrosine kinase 2 beta (Ptk2b), p21 protein (Cdc42/Rac)-activated kinase 4 (Pak4) and FYN oncogene related to SRC, FGR, YES (Fyn). The interactions between signaling pathways were further analyzed and a network was created. MAPK and calcium signaling pathways were found to be located at the center of the network. Thus, protein kinases constitute potential drug targets for AP treatment.
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1 

Voronina S, Longbottom R, Sutton R, Petersen OH and Tepikin A: Bile acids induce calcium signals in mose pancreatic acinar cells: implications for bile-induced pancreatic pathology. J Physiol. 540:49–55. 2002. View Article : Google Scholar : PubMed/NCBI

2 

Gerasimenko JV, Flowerdew SE, Voronina SG, et al: Bile acids induce Ca2+ release from both the endoplasmic reticulum and acidic intracellular calcium stores through activation of inositol trisphosphate receptors and ryanodine receptors. J Biol Chem. 281:40154–40163. 2006.PubMed/NCBI

3 

Perides G, Laukkarinen JM, Vassileva G and Steer ML: Biliary acute pancreatitis in mice is mediated by the G-protein-coupled cell surface bile acid receptor Gpbar1. Gastroenterology. 138:715–725. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Thrower EC, Gorelick FS and Husain SZ: Molecular and cellular mechanisms of pancreatic injury. Curr Opin Gastroenterol. 26:484–489. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Halangk W and Lerch MM: Early events in acute pancreatitis. Clin Lab Med. 25:1–15. 2005. View Article : Google Scholar

6 

Reiser J, Adair B and Reinheckel T: Specialized roles for cysteine cathepsins in health and disease. J Clin Invest. 120:3421–3431. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Lindkvist B, Fajardo I, Pejler G and Borgström A: Cathepsin B activates human trypsinogen 1 but not proelastase 2 or procarboxypeptidase B. Pancreatology. 6:224–231. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Wartmann T, Mayerle J, Kähne T, et al: Cathepsin L inactivates human trypsinogen, whereas cathepsin L-deletion reduces the severity of pancreatitis in mice. Gastroenterology. 138:726–737. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Shah AU, Sarwar A, Orabi AI, et al: Protease activation during in vivo pancreatitis is dependent on calcineurin activation. Am J Physiol Gastrointest Liver Physiol. 297:G967–G973. 2009. View Article : Google Scholar : PubMed/NCBI

10 

Gerasimenko JV, Lur G, Sherwood MW, et al: Pancreatic protease activation by alcohol metabolite depends on Ca2+ release via acid store IP3 receptors. Proc Natl Acad Sci USA. 106:10758–10763. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Weber H, Hühns S, Lüthen F and Jonas L: Calpain-mediated breakdown of cytoskeletal proteins contributes to cholecystokinin-induced damage of rat pancreatic acini. Int J Exp Pathol. 90:387–399. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Husain SZ, Prasad P, Grant WM, Kolodecik TR, Nathanson MH and Gorelick FS: The ryanodine receptor mediates early zymogen activation in pancreatitis. Proc Natl Acad Sci USA. 102:14386–14391. 2005. View Article : Google Scholar : PubMed/NCBI

13 

Thrower EC, Yuan J, Usmani A, et al: A novel protein kinase D inhibitor attenuates early events of experimental pancreatitis in isolated rat acini. Am J Physiol Gastrointest Liver Physiol. 300:G120–G129. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Awla D, Hartman H, Abdulla A, et al: Rho-kinase signalling regulates trypsinogen activation and tissue damage in severe acute pancreatitis. Br J Pharmacol. 162:648–658. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Namkung W, Yoon JS, Kim KH and Lee MG: PAR2 exerts local protection against acute pancreatitis via modulation of MAP kinase and MAP kinase phosphatase signaling. Am J Physiol Gastrointest Liver Physiol. 295:G886–G894. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Gorelick F, Pandol S and Thrower E: Protein kinase C in the pancreatic acinar cell. J Gastroenterol Hepatol. 23:S37–S41. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Li Z, Lu M, Chu J, Qiao X, Meng X, Sun B, Zhang W and Xue D: Early proteome analysis of rat pancreatic acinar AR42J cells treated with taurolithocholic acid 3-sulfate. Pancreatology. 12:248–256. 2012. View Article : Google Scholar : PubMed/NCBI

18 

Andrzejewska A and Dlugosz JW: Differential effects of endothelins on histological and ultrastructural changes and trypsinogen activation in the secretagogue-induced acute pancreatitis in rats. Exp Toxicol Pathol. 63:371–378. 2011. View Article : Google Scholar

19 

Andrzejewska A, Dlugosz JW and Augustynowicz A: Effect of endothelin-1 receptor antagonists on histological and ultrastructural changes in the pancreas and trypsinogen activation in the early course of caerulein-induced acute pancreatitis in rats. World J Gastroenterol. 11:1115–1121. 2005. View Article : Google Scholar

20 

Zheng XL, Kitamoto Y and Sadler JE: Enteropeptidase, a type II transmembrane serine protease. Front Biosci (Elite Ed). 1:242–249. 2009.PubMed/NCBI

21 

Hartwig W, Kolvenbach M, Hackert T, Fortunato F, Schneider L, Büchler MW and Werner J: Enterokinase induces severe necrosis and rapid mortality in cerulein pancreatitis: characterization of a novel noninvasive rat model of necro-hemorrhagic pancreatitis. Surgery. 142:327–336. 2007. View Article : Google Scholar

22 

Morel M, Couturier J, Lafay-Chebassier C, Paccalin M and Page G: PKR, the double stranded RNA-dependent protein kinase as a critical target in Alzheimer’s disease. J Cell Mol Med. 13:1476–1488. 2009.PubMed/NCBI

23 

Kanda S, Miyata Y, Kanetake H and Smithgall TE: Non-receptor protein-tyrosine kinases as molecular targets for antiangiogenic therapy. Int J Mol Med. 20:113–121. 2007.PubMed/NCBI

24 

Katoh Y and Katoh M: FGFR2-related pathogenesis and FGFR2-targeted therapeutics (Review). Int J Mol Med. 23:307–311. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Ward JB, Petersen OH, Jenkins SA and Sutton R: Is an elevated concentration of acinar cytosolic free ionized calcium the trigger for acute pancreatitis? Lancet. 346:1016–1019. 1995. View Article : Google Scholar : PubMed/NCBI

26 

Mooren FCh, Hlouschek V, Finkes T, et al: Early changes in pancreatic acinar cell calcium signaling after pancreatic duct obstruction. J Biol Chem. 278:9361–9369. 2003. View Article : Google Scholar : PubMed/NCBI

27 

Frick TW: The role of calcium in acute pancreatitis. Surgery. 152:S157–S163. 2012. View Article : Google Scholar : PubMed/NCBI

28 

Kim JY, Kim KH, Lee JA, et al: Transporter-mediated bile acid uptake causes Ca2+-dependent cell death in rat pancreatic acinar cells. Gastroenterology. 122:1941–1953. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Raraty M, Ward J, Erdemil G, Vaillant C, Neoptolemos JP, Sutton R and Petersen OH: Calcium-dependent enzyme activation and vacuole formation in the apical granular region of pancreatic acinar cells. Proc Natl Acad Sci USA. 97:13126–13131. 2000. View Article : Google Scholar : PubMed/NCBI

30 

Ozawa T: FK506 induces biphasic Ca2+ release from microsomal vesicles of rat pancreatic acinar cells. Int J Mol Med. 18:187–191. 2006.PubMed/NCBI

31 

Kessen U, Schaloske R, Aichem A and Mutzel R: Ca(2+)/calmodulin-independent activation of calcineurin from Dictyostelium by unsaturated long chain fatty acids. J Biol Chem. 274:37821–37826. 1999.

32 

Conze D, Krahl T, Kennedy N, et al: c-Jun NH(2)-terminal kinase(JNK)1 and JNK2 have distinct roles in CD8(+) T cell activation. J Exp Med. 195:811–823. 2002.

33 

Yang J, Murphy C, Denham W, Botchkina G, Tracey KJ and Norman J: Evidence of a central role for p38 map kinase induction of tumor necrosis factor alpha in pancreatitis-associated pulmonary injury. Surgery. 126:216–222. 1999. View Article : Google Scholar : PubMed/NCBI

34 

Pereda J, Sabater L, Cassinello N, et al: Effect of simultaneous inhibition of TNF-alpha production and xanthine oxidase in experimental acute pancreatitis: the role of mitogen activated protein kinases. Ann Surg. 240:108–116. 2004. View Article : Google Scholar

35 

Araki Y, Andoh A, Yokono T, et al: The free radical scavenger edaravone suppresses experimental closed duodenal loop-induced acute pancreatitis in rats. Int J Mol Med. 12:121–124. 2003.PubMed/NCBI

36 

Williard DE, Twait E, Yuan Z, Carter AB and Samuel I: Nuclear factor kappa B-dependent gene transcription in cholecystokinin and tumor necrosis factor-alpha-stimulated isolated acinar cells is regulated by p38 mitogen-activated protein kinase. Am J Surg. 200:283–290. 2010. View Article : Google Scholar

37 

Samuel I, Zaheer S, Fisher RA and Zaheer A: Cholinergic receptor induction and JNK activation in acute pancreatitis. Am J Surg. 186:569–574. 2003. View Article : Google Scholar : PubMed/NCBI

38 

Liu HS, Pan CE, Liu QG, Yang W and Liu XM: Effect of NF-kappaB and p38 MAPK in activated monocytes/macrophages on pro-inflammatory cytokines of rats with acute pancreatitis. World J Gastroenterol. 9:2513–2518. 2003.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ma B, Wu L, Lu M, Gao B, Qiao X, Sun B, Xue D and Zhang W: Differentially expressed kinase genes associated with trypsinogen activation in rat pancreatic acinar cells treated with taurolithocholic acid 3-sulfate. Mol Med Rep 7: 1591-1596, 2013.
APA
Ma, B., Wu, L., Lu, M., Gao, B., Qiao, X., Sun, B. ... Zhang, W. (2013). Differentially expressed kinase genes associated with trypsinogen activation in rat pancreatic acinar cells treated with taurolithocholic acid 3-sulfate. Molecular Medicine Reports, 7, 1591-1596. https://doi.org/10.3892/mmr.2013.1355
MLA
Ma, B., Wu, L., Lu, M., Gao, B., Qiao, X., Sun, B., Xue, D., Zhang, W."Differentially expressed kinase genes associated with trypsinogen activation in rat pancreatic acinar cells treated with taurolithocholic acid 3-sulfate". Molecular Medicine Reports 7.5 (2013): 1591-1596.
Chicago
Ma, B., Wu, L., Lu, M., Gao, B., Qiao, X., Sun, B., Xue, D., Zhang, W."Differentially expressed kinase genes associated with trypsinogen activation in rat pancreatic acinar cells treated with taurolithocholic acid 3-sulfate". Molecular Medicine Reports 7, no. 5 (2013): 1591-1596. https://doi.org/10.3892/mmr.2013.1355
Copy and paste a formatted citation
x
Spandidos Publications style
Ma B, Wu L, Lu M, Gao B, Qiao X, Sun B, Xue D and Zhang W: Differentially expressed kinase genes associated with trypsinogen activation in rat pancreatic acinar cells treated with taurolithocholic acid 3-sulfate. Mol Med Rep 7: 1591-1596, 2013.
APA
Ma, B., Wu, L., Lu, M., Gao, B., Qiao, X., Sun, B. ... Zhang, W. (2013). Differentially expressed kinase genes associated with trypsinogen activation in rat pancreatic acinar cells treated with taurolithocholic acid 3-sulfate. Molecular Medicine Reports, 7, 1591-1596. https://doi.org/10.3892/mmr.2013.1355
MLA
Ma, B., Wu, L., Lu, M., Gao, B., Qiao, X., Sun, B., Xue, D., Zhang, W."Differentially expressed kinase genes associated with trypsinogen activation in rat pancreatic acinar cells treated with taurolithocholic acid 3-sulfate". Molecular Medicine Reports 7.5 (2013): 1591-1596.
Chicago
Ma, B., Wu, L., Lu, M., Gao, B., Qiao, X., Sun, B., Xue, D., Zhang, W."Differentially expressed kinase genes associated with trypsinogen activation in rat pancreatic acinar cells treated with taurolithocholic acid 3-sulfate". Molecular Medicine Reports 7, no. 5 (2013): 1591-1596. https://doi.org/10.3892/mmr.2013.1355
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