Abstract
Mitogen-activated protein kinases have been shown to respond to various stimuli including cytokines, mitogens and gamma irradiation, leading to cell proliferation, differentiation, or death. The duration of their activation determines the specificity of response to each stimulus in various cells. In this study, the crucial intracellular kinases, ERK, JNK, and p38 kinase involved in cell survival, death, or damage and repair were examined for their activity in RAW 264.7 cells at various time points after irradiation with 2 Gy doses of proton ions or X-rays. This is the first report that shows that the MAPK signaling induced after heavy ion or X-ray exposure is not the same. Unlike gamma irradiation, there was prolonged but marginal activation of prosurvival ERK pathway and significant activation of proapoptotic p38 pathway in response to high LET radiation.
References
Dent P, Yacoub A, Fisher PB, Hagan MP, Grant S (2003) MAPK pathways in radiation responses. Oncogene 22(37):5885–5896
Narang H, Krishna M (2004) Mitogen activated protein kinases: specificity of response to dose of ionising radiation in Liver. J Radiat Res (Tokyo) 45:1–8. doi:10.1269/jrr.45.213
Narang H, Krishna M (2008) Effect of nitric oxide donor and gamma irradiation on MAPK signaling in murine peritoneal macrohages. J Cell Biochem 103(2):576–587. doi:10.1002/jcb.21429
Schmidt-Ullrich RK, Valerie K, Fogleman B, Walters J (1996) The radiation-induced autophosphorylation of epidermal growth factor receptor in human malignant mammary and squamous epithelial cells. Radiat Res 145:81–86. doi:10.2307/3579199
Schmidt-Ullrich RK, Mikkelsen RB, Dent P, Todd DG, Valerie K, Kavanagh BD, Contessa JN, Rorrer WK, Chen PB (1997) Radiation-induced proliferation of human A431 squamous carcinoma cells is dependent on EGFR tyrosine phosphorylation. Oncogene 15:1191–1197. doi:10.1038/sj.onc.1201275
Munster PN, Marchion DC, Basso AD, Rosen N (2002) Degradation of HER2 by ansamycins induces growth arrest and apoptosis in cells with HER2 overexpression via a HER3, phosphatidylinositol 3′-kinase-AKT-dependent pathway. Cancer Res 62:3132–3137
Contessa JN, Reardon DB, Todd D, Dent P, Mikkelsen RB, Valerie K, Bowers GD, Schmidt-Ullrich RK (1999) The inducible expression of dominant negative epidermal growth factor receptor CD533 in radiosensitization of human mammary carcinoma cells. Clin Cancer Res 5:405–411
Baselga J, Norton L, Albanell J, Kim YM, Mendelsohn J (1998) Recombinant humanized anti-HER2 antibody (Herceptin) enhances the antitumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts. Cancer Res 58:2825–2831
Huang S-M, Bock JM, Harari PM (1999) Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. Cancer Res 59:1935–1940
Wang X, McGowan CH, Zhao M, He L, Downey JS, Fearns C, Wang Y, Huang S, Han J (2000) Involvement of the MKK6–p38gamma cascade in gamma-radiation-induced cell cycle arrest. Mol Cell Biol 20:4543–4552. doi:10.1128/MCB.20.13.4543-4552.2000
English J, Pearson G, Wilsbacher J, Swantek J, Karandikar M, Xu S, Cobb MH (1999) New insights into the control of MAP kinase pathways. Exp Cell Res 253:255–270. doi:10.1006/excr.1999.4687
Kovalovsky D, Refojo D, Holsboer F, Arzt E (2000) Molecular mechanisms and Th1/Th2 pathways in corticosteroid regulation of cytokine production. J Neuroimmunol 109:23–29. doi:10.1016/S0165-5728(00)00298-8
Bellmann K, Burkart V, Bruckhoff J, Kolb H, Landry J (2000) p38-dependent enhancement of cytokine induced nitric oxide synthase gene expression by heat shock protein 70. J Biol Chem 275:18172–18179. doi:10.1074/jbc.M000340200
Ebisuya M, Kondoh K, Nishida E (2005) The duration, magnitude and compartmentalization of ERK MAP kinase activity: mechanisms for providing signaling specificity. J Cell Sci 118:2997–3002. doi:10.1242/jcs.02505
Hall EJ (2000) Radiobiology for the radiologist, 5th edn. Lippincott, Philadelphia, pp 5–17
Goto S, Watanabe M, Yatagai F (2002) Delayed cell cycle progression in human lymphoblastoid cells after exposure to high-LET radiation correlates with extremely localized DNA damage. Radiat Res 158(6):678–686. doi:10.1667/0033-7587(2002)158[0678:DCCPIH]2.0.CO;2
Mitra AK, Sarma A, Krishna M, Verma NC (2004) Expression of NF-kB and ERK following heavy ion irradiation. J Env Path Toxicol Onc 23:53–59. doi:10.1615/JEnvPathToxOncol.v23.i1.50
Goodhead DT (1989) The initial physical damage produced by ionizing radiations. Int J Radiat Biol 56(5):623–634
Blakely EA, Kronenberg A (1998) Heavy-ion radiobiology: new approaches to delineate mechanisms underlying enhanced biological effectiveness. Radiat Res 150:S126–S245. doi:10.2307/3579815
Nakano T, Suzuki Y, Ohno T et al (2006) Carbon beam therapy overcomes the radiation resistance of uterine cervical cancer originating from hypoxia. Clin Cancer Res 12:2185–2219. doi:10.1158/1078-0432.CCR-05-1907
Hamadaa N, Haraa T, Omura-Minamisawad M, Funayamac T, Sakashitac T, Soraa S, Yokotac Y, Nakanob T, Kobayashia Y (2008) Energetic heavy ions overcome tumor radioresistance caused by overexpression of Bcl-2. Radiother Oncol 89(2):231–236. doi:10.1016/j.radonc.2008.02.013
Kim SJ, Ju JW, Oh CD, Yoon YM, Song WK, Kim JH, Yoo YJ, Bang OS, Kang SS (2002) ERK-1/2 and p38 kinase oppositely regulate nitric oxide-induced apoptosis of chondrocytes in association with p53, caspase-3, and differentiation status. J Biol Chem 277:1332–1339. doi:10.1074/jbc.M107231200
Taher MM, Hershey CM, Oakley JD, Valerie K (2000) Role of the p38 and MEK-1/2/p42/44 MAP kinase pathways in the differential activation of human immunodeficiency virus gene expression by ultraviolet and ionizing radiation. Photochem Photobiol 71:455–459. doi:10.1562/0031-8655(2000)071<0455:ROTPAM>2.0.CO;2
Lee YJ, Soh JW, Dean NM, Cho CK, Kim TH, Lee SJ, Lee YS (2002) Protein kinase C delta over expression enhances radiation sensitivity via extracellular regulated protein kinase 1/2 activation, abolishing the radiation-induced G(2)-M arrest. Cell Growth Differ 13:237–246
Bulavin DV, Amundson SA, Fornace AJ (2002) p38 and Chk1 kinases: different conductors for the G(2)/M checkpoint symphony. Curr Opin Genet Dev 12:92–97. doi:10.1016/S0959-437X(01)00270-2
Scholz M, Kraft-Weyrather W, Ritter S, Kraft G (1994) Cell cycle delays induced by heavy ion irradiation of synchronous mammalian cells. Int J Radiat Biol 66:59–75. doi:10.1080/09553009414550951
Klotz L-O, Brivada K, Sies H (2000) Signaling by singlet oxygen in biological systems. In: Antioxidant and redox regulation of genes. Academic Press, San Diego, pp 3–20
Klotz LO, Pellieux C, Briviba K, Pierlot C, Aubry JM, Sies H (1999) Mitogen-activated protein kinase (p38-, JNK-, ERK-) activation pattern induced by extracellular and intracellular singlet oxygen and UVA. Eur J Biochem 260:917–922. doi:10.1046/j.1432-1327.1999.00255.x
Guyton KZ, Liu Y, Gorospe M, Xu Q, Holbrook NJ (1996) Activation of mitogen-activated protein kinase by H2O2. Role in cell survival following oxidant injury. J Biol Chem 271:4138–4142. doi:10.1074/jbc.271.7.3604
Schieke SM, Briviba K, Klotz LO, Sies H (1999) Activation pattern of mitogen-activated protein kinases elicited by peroxynitrite: attenuation by selenite supplementation. FEBS Lett 448:301–303. doi:10.1016/S0014-5793(99)00372-5
Murakami T, Takagi H, Suzuma K, Suzuma I, Ohashi H, Watanabe D, Ojima T, Suganami E, Kurimoto M, Kaneto H, Honda Y, Yoshimura N (2005) Angiopoietin-1 attenuates H2O2-induced SEK1/JNK phosphorylation through the phosphatidylinositol 3-kinase/Akt pathway in vascular endothelial cells. J Biol Chem 280:31841–31849. doi:10.1074/jbc.M503108200
Kamata H, Honda S, Maeda S, Chang L, Hirata H, Karin M (2005) Reactive oxygen species promote TNF alpha induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell 120:649–661. doi:10.1016/j.cell.2004.12.041
Sumbayev VV and Yasinska IM (2005) Regulation of MAP kinase-dependent apoptotic pathway: implication of reactive oxygen and nitrogen species 436: 406–412
Handrick R, Rubel A, Faltin H, Eibl H, Belka C, Jendrossek V (2006) Increased cytotoxicity of ionizing radiation in combination with membrane-targeted apoptosis modulators involves downregulation of protein kinase B/Akt-mediated survival-signaling. Radiother Oncol 80:199–206. doi:10.1016/j.radonc.2006.07.021
Wissink EH, Verbrugge I, Vink SR, Schader MB, Schaefer U, Walczak H, Borst J, Verheij M (2006) TRAIL enhances efficacy of radiotherapy in a p53 mutant, Bcl-2 overexpressing lymphoid malignancy. Radiother Oncol 80:214–222. doi:10.1016/j.radonc.2006.07.030
Kasten-Pisula U, Windhorst S, Dahm-Daphi J, Mayr G, Dikomey E (2007) Radiosensitization of tumour cell lines by the polyphenol gossypol results from depressed double-strand break repair and not from enhanced apoptosis. Radiother Oncol 83:296–303. doi:10.1016/j.radonc.2007.04.024
Overgaard J, Baumann M (2007) Translational research in radiotherapy–getting closer to the bedside. Radiother Oncol 83:217–219. doi:10.1016/j.radonc.2007.06.001
Linstadt D, Blakely E, Phillips TL, Castro JR (1988) Radiosensitization produced by iododeoxyuridine with high linear energy transfer heavy ion beams. Int J Radiat Oncol Biol Phys 15:703–710
Kitabayashi H, Shimada H, Yamada S, Yasuda S, Kamata T, Ando K, Tsujii H, Ochiai T (2006) Synergistic growth suppression induced in esophageal squamous cell carcinoma cells by combined treatment with docetaxel and heavy carbon ion beam irradiation. Oncol Rep 15:913–918
Liu B, Zhang H, Zhou G, Xie Y, Hao J, Qiu R, Duan X, Zhou Q (2007) Adenovirus-mediated p53 gene transfer sensitizes hepatocellular carcinoma cells to heavy-ion radiation. J Gastroenterol 42:140–145. doi:10.1007/s00535-006-1977-9
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Narang, H., Bhat, N., Gupta, S.K. et al. Differential activation of mitogen-activated protein kinases following high and low LET radiation in murine macrophage cell line. Mol Cell Biochem 324, 85–91 (2009). https://doi.org/10.1007/s11010-008-9987-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-008-9987-y