Artículo

Este artículo es de Acceso Abierto y puede ser descargado en su versión final desde nuestro repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Background: Chronic injury deregulates cellular homeostasis and induces a number of alterations leading to disruption of cellular processes such as cell cycle checkpoints and apoptosis, driving to carcinogenesis. The stress protein heme oxygenase-1 (HO-1) catalyzes heme degradation producing biliverdin, iron and CO. Induction of HO-1 has been suggested to be essential for a controlled cell growth. The aim of this work was to analyze the in vivo homeostatic response (HR) triggered by the withdrawal of a potent carcinogen, p-dimethylaminoazobenzene (DAB), after preneoplastic lesions were observed. We analyzed HO-1 cellular localization and the expression of HO-1, Bcl-2 and cell cycle related proteins under these conditions comparing them to hepatocellular carcinoma (HC). Methods: The intoxication protocol was designed based on previous studies demonstrating that preneoplastic lesions were evident after 89 days of chemical carcinogen administration. Male CF1 mice (n = 18) were used. HR group received DAB (0.5 % w/w) in the diet for 78 days followed by 11 days of carcinogen deprivation. The HC group received the carcinogen and control animals the standard diet during 89 days. The expression of cell cycle related proteins, of Bcl-2 and of HO-1 were analyzed by western blot. The cellular localization and expression of HO-1 were detected by immnunohistochemistry. Results: Increased expression of cyclin E/CDK2 was observed in HR, thus implicating cyclin E/CDK2 in the liver regenerative process. p21cip1/waf1 and Bcl-2 induction in HC was restituted to basal levels in HR. A similar response profile was found for HO-1 expression levels, showing a lower oxidative status in the carcinogen-deprived liver. The immunohistochemical studies revealed the presence of macrophages surrounding foci of necrosis and nodular lesions in HR indicative of an inflammatory response. Furthermore, regenerative cells displayed changes in type, size and intensity of HO-1 immunostaining. Conclusion: These results demonstrate that the regenera tive capacity of the liver is still observed in the pre-neoplastic tissue after carcinogen withdrawal suggesting that reversible mechanism/s to compensate necrosis and to restitute homeostasis are involved. © 2006 Castronuovo et al; licensee BioMed Central Ltd.

Registro:

Documento: Artículo
Título:Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association
Autor:Castronuovo, C.C.; Sacca, P.A.; Meiss, R.; Caballero, F.A.; Batlle, A.; Vazquez, E.S.
Filiación:Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón II - 4to Piso, 1428 Buenos Aires, Argentina
Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), Hospital de Clínicas, Universidad de Buenos Aires, Pabellón II - 4to Piso, 1428 Buenos Aires, Argentina
Departamento de Patología, Instituto de Estudios Oncológicos, Academia Nacional de Medicina, Pacheco de Melo 3081, 1425 Buenos Aires, Argentina
Palabras clave:4 dimethylaminoazobenzene; carcinogen; cell cycle protein; cyclin dependent kinase 2; cyclin dependent kinase inhibitor 1; cyclin E; heme oxygenase 1; protein bcl 2; animal cell; animal experiment; animal model; animal tissue; article; cell type; cellular distribution; controlled study; dietary intake; enzyme analysis; hepatitis; homeostasis; immunohistochemistry; in vivo study; liver cell carcinoma; liver necrosis; liver regeneration; macrophage; male; mouse; mouse strain; nonhuman; oxidative stress; protein expression; protein induction; Western blotting; Animals; Carcinogens; Carcinoma, Hepatocellular; Cell Cycle; Cell Cycle Proteins; Drug Administration Schedule; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Heme Oxygenase-1; Homeostasis; Liver Neoplasms; Male; Mice; Mice, Inbred Strains; p-Dimethylaminoazobenzene
Año:2006
Volumen:6
DOI: http://dx.doi.org/10.1186/1471-2407-6-286
Título revista:BMC Cancer
Título revista abreviado:BMC Cancer
ISSN:14712407
CODEN:BCMAC
CAS:4 dimethylaminoazobenzene, 60-11-7; cyclin dependent kinase 2, 141349-86-2; protein bcl 2, 219306-68-0; Carcinogens; Cell Cycle Proteins; Heme Oxygenase-1, 1.14.99.3; p-Dimethylaminoazobenzene, 60-11-7
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_14712407_v6_n_p_Castronuovo.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14712407_v6_n_p_Castronuovo

Referencias:

  • Cha, C., Dematteo, R.P., Molecular mechanisms in hepatocellular carcinoma development (2005) Best Pract Res Clin Gastroenetrol, 19, pp. 25-37. , 10.1016/j.bpg.2004.11.005
  • Bralet, M.P., Pichard, V., Ferry, N., Demostration of direct lineage between hepatocytes and hepatocellular carcinoma in diethynitrosamina-trated rats (2002) Hepatology, 36, pp. 623-630. , 10.1053/jhep.2002.35540 12198654
  • Espandiari, P., Robertson, L.W., Srinivasan, C., Glauert, H.P., Comparison of different initiation protocols in the resistant hepatocyte model (2005) Toxicology, 206, pp. 373-381. , 10.1016/j.tox.2004.07.014 15588927
  • Minuk, G.Y., Hepatic regeneration: If it ain't broke, don't fix it (2003) Can J Gastroenterol, 17, pp. 418-424. , 12915914
  • Fausto, M., Campbell, J.S., The role of hepatocytes and oval cells in liver regeneration and repopulation (2003) Mech Dev, 120, pp. 117-130. , 10.1016/S0925-4773(02)00338-6 12490302
  • Alison, M.R., Regulation of hepatic growth (1986) Physiol Rev, 66, pp. 499-541. , 2426724
  • Kountouras, J., Boura, P., Lygidakis, N.J., Liver regeneration after hepatectomy (2001) Hepatogastroenterology, 48, pp. 556-562. , 11379353
  • Nam, S.W., Park, J.Y., Ramasamy, A., Shevade, S., Islam, A., Long, P.M., Park, C.K., Lee, J.Y., Molecular changes from dysplastic nodule to hepatocellular carcinoma through gene expression profiling (2005) Hepatology, 42, pp. 809-818. , 10.1002/hep.20878 16175600
  • Hui, A.M., Makuuchi, M., Li, X., Cell cycle regulators ad human hepatocarcinogenesis (1998) Hepatogastroenterology, 45, pp. 1635-1642. , 9840120
  • Sacca, P., Caballero, F., Batlle, A., Vazquez, E., Cell cycle arrest and modulation of HO-1 expression induced by acetyl salicylic acid in hepatocarcinogenesis (2004) Int J Biochem Cell Biol, 36, pp. 1945-1953. , 10.1016/j.biocel.2004.01.029 15203109
  • Senderowicz, A.M., Small-molecule cyclin-dependent kinase modulators (2003) Oncogene, 22, pp. 6609-6620. , 10.1038/sj.onc.1206954 14528286
  • Inguaggiato, P., Gonzalez-Michaca, L., Croatt, J., Haggard, J., Alam, J., Nath, K., Cellular overexpression of heme oxygenase-1 up-regulates p21cip1/waf1 and confers resistance to apoptosis (2001) Kidney International, 60, pp. 2181-2191. , 10.1046/j.1523-1755.2001.00046.x 11737592
  • Gerez, E., Vazquez, E., Caballero, F., Polo, C., Batlle, A., Altered heme pathway regulation and drug metabolizing enzyme system in a mouse model of hepatocarcinogenesis: Effect of veronal (1997) Gen Pharmacol, 29, pp. 569-573. , 10.1016/S0306-3623(96)00574-5 9352304
  • Caballero, F., Meiss, R., Giménez, A., Batlle, A., Vazquez, E., Immunohistochemical analysis of heme oxygenase-1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis (2004) In J Exp Path, 85, pp. 213-222. , 10.1111/j.0959-9673.2004.00391.x
  • Frith, C., Ward, J., Turusov, V., Tumours of the liver: Tumours of the mouse (1994) Pathology of Tumours in Laboratory Animals, 2, pp. 223-269. , Lyon: IARC Scientific Publications No. 111, International Agency for Research on Cancer Turusov V, Mohr U
  • Knight, B., Yeoh, G.C., TNF/LT alpha double knockout mice display abnormal inflammatory and regenerative responses to acute and chronic liver injury (2005) Cell Tissue Res, 319, pp. 61-70. , 10.1007/s00441-004-1003-6 15592751
  • Choi, A.M., Alam, J., Heme oxygenase-1: Function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury (1996) Am J Respir Cell Mol Biol, 15, pp. 9-19. , 8679227
  • Hayashi, S., Takamiya, R., Yamaguchi, T., Matsumoto, K., Tojo, S.J., Tamatani, T., Kitajima, M., Suematsu, M., Induction of heme oxygenase-1 suppresses venular leukocyte adhesion elicited by oxidative stress: Role of bilirubin generated by the enzyme (1999) Circ Res, 85, pp. 663-671. , 10521239
  • Vazquez, E., Geréz, E., Caballero, F., Olivieri, L., Falcoff, N., Tomaro, M.L., Batlle, A., On the promoting action of tamoxifen in the p-dimethylaminoazobencene induced hepatocarcinogenesis CF1 mice model and the cytoprotective role of heme oxygenase (2002) Heme Oxygenase in Biology and Medicine, pp. 469-479. , New York, Boston, Dordrecht, London, Moscow: Kluwer Academic/Plenum Publishers Abraham NG, Alan J, Nath K
  • Molto, L., Rayman, P., Paszkiewicz, E., Thornton, M., Resse, L., Thomas, J.C., Das, T., Tannenbaum, C., The Bcl-2 transgene protects T cell from renal cell carcinoma-mediated apoptosis (2003) Clin Cancer Res, 9, pp. 4060-4068. , 14519627
  • Ruvolo, P., Deng, X., May, W.S., Phosphorylation of Bcl2 and regulation of apoptosis (2001) Leukemia, 15, pp. 515-522. , 10.1038/sj.leu.2402197 11368354
  • Gladden, A., Diehl, J.A., Cell cycle progression without cyclin E/CDK2: Breaking down the walls of dogma (2003) Cancer Cell, 4, pp. 160-162. , 10.1016/S1535-6108(03)00217-4 14522248
  • Maines, M., Gibbs, P., 30 some years of heme oxygenase: From a "molecular wrecking ball" to a "mesmerizing" trigger of cellular events (2005) Biochem Biophys Res Commun, 338, pp. 568-577. , 10.1016/j.bbrc.2005.08.121 16183036
  • Alam, J., Igarashi, K., Immenschuh, S., Shibahara, S., Tyrrell, R., Regulation of heme oxygenase-1 gene transcription: Recent advances and highlights from the International Conference (Uppsala, 2003) on Heme Oxygenase (2004) Antiox Redox, 6, pp. 924-933
  • Dulak, J., Loboda, A., Zagorska, A., Jozkowicz, A., Complex role of heme oxygenase-1 in angiogenesis (2004) Antiox Redox Signal, 6, pp. 858-866
  • Wang, L., Lee, T., Pai, R., Chau, L., Expression of heme oxygenase-1 in atherosclerosis lesions (1998) Am J Pathol, 152, pp. 711-720. , 9502413
  • Katori, M., Buelow, R., Ke, B., Ma, J., Coito, A.J., Iyer, S., Southard, D., Kupiec-Weglinski, J.W., Heme oxygenase-1 overexpression protects rat hearts from cold ischemia/ reperfusion injury via an antiapoptotic pathway (2002) Transplantation, 73, pp. 287-292. , 10.1097/00007890-200201270-00023 11821745
  • Coito, A.J., Buelow, R., Shen, X.D., Amersi, F., Moore, C., Volk, H.D., Busuttil, R.W., Kupiec-Weglinski, J.W., Heme oxygenase-1 gene transfer inhibits inducible nitric oxide synthase expression and protects genetically fat Zucker rat livers from ischemia-reperfusion injury (2002) Transplantation, 74, pp. 96-102. , 10.1097/00007890-200207150-00017 12134106
  • Abraham, N.G., Drummond, G.S., Lutton, J.D., Kappas, A., The biological significance and physiological role of heme oxygenase (1996) Cell Physiol Biochem, 6, pp. 129-168
  • Deramaudt, B.M., Braunstein, S., Remy, P., Abraham, N.G., Gene transfer of human heme oxygenase into coronary endothelial cells potentially promotes angiogenesis (1998) J Cell Biochem, 68, pp. 121-127. , 10.1002/(SICI)1097-4644(19980101)68:1<121::AID-JCB12>3.0.CO;2-K 9407320
  • Otterbein, L.E., Soares, M.P., Yamashita, K., Bach, F.H., Heme oxygenase-1: Unleashing the protective properties of heme (2003) Trends of Immunology, 24, pp. 449-455. , 10.1016/S1471-4906(03)00181-9
  • Bussolati, B., Ahmed, A., Pemberton, H., Landis, R.C., Di Carlo, F., Haskard, D.O., Mason, J.C., Bifuncional role for VEGF-induced heme oxygenase-1 in vivo: Induction of angiogenesis and inhibition of leukocytic infiltration (2004) Blood, 103, pp. 761-766. , 10.1182/blood-2003-06-1974 14525760
  • Fernandez, M., Bonkovsky, H.L., Increased heme oxygenase-1 gene expression in liver cells and splanchnic organs from portal hypertensive rats (1999) Hepatology, 29, pp. 1672-1679. , 10.1002/hep.510290621 10347107
  • Nakao, A., Neto, J.S., Kanno, S., Stolz, D.B., Kimizuka, K., Liu, F., Bach, F.H., Noriko, M., Protection against ischemia/reperfusion injury in cardiac and renal transplantation with carbon monoxide, biliverdin and both (2005) Am J Transplant, 5, pp. 282-291. , 10.1111/j.1600-6143.2004.00695.x 15643987
  • Otterbein, L.E., Lee, P.J., Chin, B.Y., Petrache, I., Camhi, S.L., Alam, J., Choi, A.M., Protective effects of heme oxygenase-1 in acute lung injury (1999) Chest, 116, pp. 61S-63S. , 10.1378/chest.116.suppl_1.61S-a 10424595
  • Ghaziani, T., Shan, Y., Lambrecht, R., Donohue, S., Pietschmann, T., Bartenschlager, R., Bonkovsky, H.L., HCV proteins increase expression of heme oxygenase-1 (HO-1) and decrease expression of Bach1 in human hepatoma cells (2006) J Hepatol, 45, pp. 5-12. , 10.1016/j.jhep.2005.12.020 16530877

Citas:

---------- APA ----------
Castronuovo, C.C., Sacca, P.A., Meiss, R., Caballero, F.A., Batlle, A. & Vazquez, E.S. (2006) . Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association. BMC Cancer, 6.
http://dx.doi.org/10.1186/1471-2407-6-286
---------- CHICAGO ----------
Castronuovo, C.C., Sacca, P.A., Meiss, R., Caballero, F.A., Batlle, A., Vazquez, E.S. "Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association" . BMC Cancer 6 (2006).
http://dx.doi.org/10.1186/1471-2407-6-286
---------- MLA ----------
Castronuovo, C.C., Sacca, P.A., Meiss, R., Caballero, F.A., Batlle, A., Vazquez, E.S. "Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association" . BMC Cancer, vol. 6, 2006.
http://dx.doi.org/10.1186/1471-2407-6-286
---------- VANCOUVER ----------
Castronuovo, C.C., Sacca, P.A., Meiss, R., Caballero, F.A., Batlle, A., Vazquez, E.S. Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association. BMC Cancer. 2006;6.
http://dx.doi.org/10.1186/1471-2407-6-286