MMSL 2012, 81(2):68-75 | DOI: 10.31482/mmsl.2012.009

EFFECT OF SOMAN ON JNK AND P38 MITOGEN ACTIVATED PROTEIN KINASE (MAPK) PATHWAYSOriginal article

Jaroslav Pejchal ORCID...1*, Jan Österreicher2, Jiří Kassa ORCID...3, Václav Mařák1, Aleš Tichý ORCID...2, Zuzana Šinkorová ORCID...2, Lenka Zárybnická ORCID...2, Klára Kubelková ORCID...1, Kamil Kuča ORCID...1
1 Center of Advanced Studies, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic
2 Department of Radiation Biology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic
3 Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic

The purpose of our study was to examine an early activation of JNK and p38 mitogen activated protein kinases (MAPK) and their substrate c-Myc after soman poisoning in order to enlighten the pathogenetic mechanism of nerve agent-induced non-specific effects. Male Wistar rats were intramuscularly poisoned by soman (60 μg.kg-1 - 70% LD50). Samples were taken 4, 24, and 72 hours after poisoning, immunohistochemically stained and phospho-JNKThr-183/Tyr-185, phospho-p38Thr180/Tyr182, and phospho-c-MycThr58/Ser62 expressions were measured using a computer Image analysis in apical and cryptal enterocytes of the colon transversum. We observed decreased phospho-JNK in apical enterocytes 4 and 24 h after poisoning and increased phospho-JNK in cryptal and apical enterocytes 72 h after intoxication. Phospho-p38 dropped significantly in the apical compartment 72 h after soman poisoning. An activation of c-Myc decreased in both apical and cryptal compartment 4 and 24 h after soman intoxication, while increased in both compartments 72 h after poisoning. Soman poisoning seems to temporarily suppress promitotic pathways of proliferating cryptal cells and causes delayed activation of JNK stress signaling pathway.

Keywords: soman; JNK, p38; c-Myc; enterocyte; rat; image analysis

Received: February 19, 2012; Revised: May 18, 2012; Published: June 8, 2012  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Pejchal, J., Österreicher, J., Kassa, J., Mařák, V., Tichý, A., Šinkorová, Z., ... Kuča, K. (2012). EFFECT OF SOMAN ON JNK AND P38 MITOGEN ACTIVATED PROTEIN KINASE (MAPK) PATHWAYS. MMSL81(2), 68-75. doi: 10.31482/mmsl.2012.009
Download citation

References

  1. Marrs, T.C. Organophosphate poisoning. Pharmacol. Ther. 1993, 58, 51-66. Go to original source... Go to PubMed...
  2. Bajgar, J. Organophosphate/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis, and treatment. Adv. Clin. Chem. 2004, 38, 151-216. Go to original source... Go to PubMed...
  3. Kassa, J.; Skopec, F.; Vachek, J. The long term changes in liver DNA and total protein contents following low level sarin exposure in rats. Acta Medica (Hradec Kralove). 2000, 43, 19-22. Go to original source... Go to PubMed...
  4. Klaidman, L.K.; Adams, J.D. Jr; Cross, R.; Pazdernik, T.L.; Samson, F. Alterations in brain glutathione homeostasis induced by the nerve gas soman. Neurotox. Res. 2003, 5, 177-182. Go to original source... Go to PubMed...
  5. Pazdernik, T.L.; Emerson, M.R.; Cross, R.; Nelson, S.R.; Samson, F.E. Soman-induced seizures: limbic activity, oxidative stress and neuroprotective proteins. J. Appl. Toxicol. 2001, 21, 87-94. Go to original source... Go to PubMed...
  6. Pejchal, J.; Osterreicher, J.; Kassa, J.; Tichy, A.; Micuda, S.; Sinkorova, Z.; Zarybnicka, L. Soman poisoning alters p38 MAPK pathway in rat cerebellar Purkinje cells. J. Appl. Toxicol. 2009, 29, 338-345. Go to original source... Go to PubMed...
  7. Pejchal, J.; Osterreicher, J.; Kassa, J.; Tichý, A.; Mokrý, J. Activation of mitogen activated protein kinase (MAPK) pathways after soman poisoning in rat cerebellar granule neurons. J. Appl. Toxicol. 2008, 28, 689-693. Go to original source... Go to PubMed...
  8. Pejchal, J.; Osterreicher, J.; Kassa, J.; Tichý, A.; Sinkorova, Z.; Zarybnicka, L.; Kuca, K. Soman and VX: different effect on cellular signaling. J. Appl. Biomed. 2012, 10, 51-61. Go to original source...
  9. Osterreicher, J.; Pejchal, J.; Kassa, J. Alteration of mitogen-activated protein kinase pathway after soman poisoning. Drug Chem Toxicol. 2007, 30, 283-291. Go to original source... Go to PubMed...
  10. Johnson, G.L.; Lapadat, R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science. 2002, 298, 1911-1912. Go to original source... Go to PubMed...
  11. Raman, M.; Chen, W.; Cobb, M.H. Differential regulation and properties of MAPKs. Oncogene. 2007, 26, 3100-3112. Go to original source... Go to PubMed...
  12. Kyriakis, J.M.; Avruch, J. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol. Rev. 2001, 81, 807-869. Go to original source... Go to PubMed...
  13. Pedraza-Alva, G.; Koulnis, M.; Charland, C.; Thornton, T.; Clements, J.L.; Schlissel, M.S.; Rincon, M. Activation of p38 MAP kinase by DNA double-strand breaks in V(D)J recombination induces a G2/M cell cycle checkpoint. EMBO J. 2006, 25, 763-773.
  14. Reinhardt, H.C.; Aslanian, A.S.; Lees, J.A.; Yaffe, M.B. p53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38MAPK/MK2 pathway for survival after DNA damage. Cancer Cell. 2007, 11, 175-189. Go to original source... Go to PubMed...
  15. Roos, W.P.; Kaina, B. DNA damage-induced cell death by apoptosis. Trends Mol. Med. 2006, 12, 440-450. Go to original source... Go to PubMed...
  16. Kassa, J.; Österreicher, J.; Knizek, J.; Fusek, J.; Macela, A. The apoptosis expression in stomach, bronchi and lungs in rats poisoned with sublethal doses of soman or mevinfos - a preliminary study. Voj. Zdrav. Listy. 2001, 70, 93-96.
  17. Dragin, N.; Smani, M.; Arnaud-Dabernat, S.; Dubost, C.; Moranvillier, I.; Costet, P.; Daniel, J.Y.; Peuchant, E. Acute oxidative stress is associated with cell proliferation in the mouse liver. FEBS Lett. 2006, 580, 3845-3852. Go to original source... Go to PubMed...
  18. Brown, M.A.; Brix, K.A. Review of health consequences from high-, intermediate- and low-level exposure to organophosphorus nerve agents. J. Appl. Toxicol. 1998, 18, 393-408. Go to original source... Go to PubMed...
  19. RamaRao, G.; Bhattacharya, B.K.; Kumar, S.; Waghmare, C.K. Gene expression and phosphoprotein profile of certain key neuronal signaling proteins following soman intoxication. Toxicology. 2011, 290, 195-202. Go to original source... Go to PubMed...
  20. Gauthier, R.; Harnois, C.; Drolet, J.F.; Reed, J.C.; Vézina, A.; Vachon, P.H. Human intestinal epithelial cell survival: differentiation state-specific control mechanisms. Am. J. Physiol. Cell. Physiol. 2001, 280, 1540-1554. Go to original source... Go to PubMed...
  21. Rivard, N.; Boucher, M.J.; Asselin, C.; L'Allemain, G. MAP kinase cascade is required for p27 downregulation and S phase entry in fibroblasts and epithelial cells. Am. J. Physiol. 1999, 277, 652-664. Go to original source... Go to PubMed...
  22. Bouchard, C.; Thieke, K.; Maier, A.; Saffrich, R.; Hanley-Hyde, J.; Ansorge, W.; Reed, S.; Sicinski, P.; Bartek, J.; Eilers, M. Direct induction of cyclin D2 by Myc contributes to cell cycle progression and sequestration of p27. EMBO J. 1999, 18, 5321-5333. Go to original source... Go to PubMed...
  23. Haas, K.; Staller, P.; Geisen, C.; Bartek, J.; Eilers, M.; Möröy, T. Mutual requirement of CDK4 and Myc in malignant transformation: evidence for cyclin D1/CDK4 and p16INK4A as upstream regulators of Myc. Oncogene. 1997, 15, 179-192. Go to original source... Go to PubMed...
  24. Buchon, N.; Broderick, N.A.; Chakrabarti, S.; Lemaitre, B. Invasive and indigenous microbiota impact intestinal stem cell activity through multiple pathways in Drosophila. Genes Dev. 2009, 23, 2333-2344. Go to original source... Go to PubMed...
  25. Staley, B.K.; Irvine, K.D. Warts and Yorkie mediate intestinal regeneration by influencing stem cell proliferation. Curr. Biol. 2010, 20, 1580-1587. Go to original source... Go to PubMed...
  26. Grenier, E.; Maupas, F.S.; Beaulieu, J.F.; Seidman, E.; Delvin, E.; Sane, A.; Tremblay, E.; Garofalo, C.; Levy, E. Effect of retinoic acid on cell proliferation and differentiation as well as on lipid synthesis, lipoprotein secretion, and apolipoprotein biogenesis. Am. J. Physiol. Gastrointest. Liver Physiol. 2007, 293, 1178-1189. Go to original source... Go to PubMed...
  27. Kuntz, S.; Kunz, C.; Rudloff, S. Oligosaccharides from human milk induce growth arrest via G2/M by influencing growth-related cell cycle genes in intestinal epithelial cells. Br. J. Nutr. 2009, 101, 1306-1315. Go to original source... Go to PubMed...
  28. Laprise, P.; Chailler, P.; Houde, M.; Beaulieu, J.F.; Boucher, M.J.; Rivard, N. Phosphatidylinositol 3-kinase controls human intestinal epithelial cell differentiation by promoting adherens junction assembly and p38 MAPK activation. J. Biol. Chem. 2002, 277, 8226-8234. Go to original source... Go to PubMed...
  29. Apidianakis, Y.; Pitsouli, C.; Perrimon, N.; Rahme, L. Synergy between bacterial infection and genetic predisposition in intestinal dysplasia. Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 20883-20888. Go to original source... Go to PubMed...
  30. Shankar, B.; Krishnan, S.; Malladi, V.; Balakrishnan, A.; Williams, P.H. Outer membrane proteins of wild-type and intimin-deficient enteropathogenic Escherichia coli induce Hep-2 cell death through intrinsic and extrinsic pathways of apoptosis. Int. J. Med. Microbiol. 2009, 299, 121-132. Go to original source... Go to PubMed...
  31. Seisenbacher, G.; Hafen, E.; Stocker, H. MK2-dependent p38b signalling protects Drosophila hindgut enterocytes against JNK-induced apoptosis under chronic stress. PloS. Genet. 2011, 7, 1-14. Go to original source...
  32. Ramirez-Alcantara, V.; LoGuidice, A.; Boelsterli, U.A. Protection from diclofenac-induced small intestinal injury by the JNK inhibitor SP600125 in a mouse model of NSAID-associated enteropathy. Am. J. Physiol. Gastrointest. Liver Physiol. 2009, 297, 990-998. Go to original source... Go to PubMed...
  33. Ciclitira, P.J.; Stewart, J.; Evan, G.; Wight, D.G.; Sikora, K. Expression of c-myc oncogene in coeliac disease. J. Clin. Pathol. 1987, 40, 307-311. Go to original source... Go to PubMed...
  34. Mazzarella, G.; Stefanile, R.; Camarca, A.; Giliberti, P.; Cosentini, E.; Marano, C.; Iaquinto, G.; Giardullo, N.; Auricchio, S.; Sette, A.; Troncone, R.; Gianfrani, C. Gliadin activates HLA class I-restricted CD8+ T cells in celiac disease intestinal mucosa and induces the enterocyte apoptosis. Gastroenterology. 2008, 134, 1017-1027. Go to original source... Go to PubMed...
  35. Moss, S.F.; Attia, L.; Scholes, J.V.; Walters, J.R.; Holt, P.R. Increased small intestinal apoptosis in coeliac disease. Gut. 1996, 39, 811-817. Go to original source... Go to PubMed...
  36. Pejchal, J.; Novotný, J.; Mařák, V.; Osterreicher, J.; Tichý, A.; Vávrová, J.; Sinkorová, Z.; Zárybnická, L.; Novotná, E.; Chládek, J.; Babicová, A.; Kubelková, K.; Kuča, K. Activation of p38 MAPK and expression of TGF-β1 in rat colon enterocytes after whole body γ-irradiation. Int. J. Radiat. Biol. 2012, 88, 348-358. Go to original source... Go to PubMed...