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Abstract:

Heme oxygenase-1 (HO-1), the inducible enzyme responsible for the rate-limiting step in the heme catabolism, is expressed in AIDS-Kaposi sarcoma (KS) lesions. Its expression is up-regulated by the Kaposi sarcoma-associated herpesvirus (KSHV) in endothelial cells, but the mechanisms underlying KSHV-induced HO-1 expression are still unknown. In this study we investigated whether the oncogenic G protein-coupled receptor (KSHV-GPCR or vGPCR), one of the key KSHV genes involved in KS development, activated HO-1 expression. Here we show that vGPCR induces HO-1 mRNA and protein levels in fibroblasts and endothelial cells. Moreover, targeted knock-down gene expression of HO-1 by small hairpin RNA and chemical inhibition of HO-1 enzymatic activity by tin protoporphyrin IX (SnPP), impaired vGPCR-induced survival, proliferation, transformation, and vascular endothelial growth factor (VEGF)-A expression. vGPCR-expressing cells implanted in the dorsal flank of nude mice developed tumors with elevated HO-1 expression and activity. Chronic administration of SnPP to the implanted mice, under conditions that effectively blocked HO-1 activity and VEGF-A expression in the transplanted cells, strikingly reduced tumor growth, without apparent side effects. On the contrary, administration of the HO-1 inducer cobalt protoporphyrin (CoPP) further enhanced vGPCR-induced tumor growth. These data postulate HO-1 as an important mediator of vGPCR-induced tumor growth and suggest that inhibition of intratumoral HO-1 activity by SnPP may be a potential therapeutic strategy. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

Registro:

Documento: Artículo
Título:Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor
Autor:Marinissen, M.J.; Tanos, T.; Bolós, M.; De Sagarra, M.R.; Coso, O.A.; Cuadrado, A.
Filiación:Inst. de Invest. Biomed. A. Sols Univ. Auton. de Madrid-Consejo Sup. de Investigaciones Cientificas, Departamento de Bioquímica, Universidad Autónoma de Madrid, Madrid 28029, Spain
Departamento de Fisiología, Biología Molecular Y Celular, Facultad de Ciencias Exactas Y Naturales, Inst. de Fisiol., Biologia Molec. and Neurociencias-Consejo Nac. de Invest. Cientificas Y Tecnicas, 1428 Buenos Aires, Argentina
Inst. de Investigaciones Biomédicas A. Sols UAM-CSIC, Dept. de Bioquímica, Laboratorio C-11, Arzobispo Morcillo 4, Madrid 28029, Spain
Palabras clave:Biomedical engineering; Genes; Growth kinetics; Proteins; RNA; Tumors; Cobalt protoporphyrin (CoPP); Gene expression; Oncogenic G protein-coupled receptor; Tumor growth; Enzyme inhibition; cobalt; G protein coupled receptor; heme oxygenase 1; protoporphyrin; animal cell; article; carcinogenesis; cell proliferation; cell survival; cell transformation; controlled study; fibroblast; gene expression; genetic transfection; Human herpesvirus 8; mouse; nonhuman; priority journal; protein expression; Animals; Annexin A5; Apoptosis; Blotting, Western; Cell Proliferation; Cell Survival; Culture Media, Serum-Free; DNA; Dose-Response Relationship, Drug; Endothelial Cells; Enzyme Inhibitors; Fibroblasts; Fluorescent Antibody Technique, Indirect; Genes, Reporter; Heme; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Herpesvirus 8, Human; Immunohistochemistry; Luciferases; Metalloporphyrins; Mice; Mice, Nude; Models, Biological; Neoplasm Transplantation; Neoplasms; NIH 3T3 Cells; Promoter Regions (Genetics); Protoporphyrins; Receptors, G-Protein-Coupled; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger; Time Factors; Transfection; Up-Regulation; Vascular Endothelial Growth Factor A; Herpesviridae; Human herpesvirus 8; Mus musculus
Año:2006
Volumen:281
Número:16
Página de inicio:11332
Página de fin:11346
DOI: http://dx.doi.org/10.1074/jbc.M512199200
Título revista:Journal of Biological Chemistry
Título revista abreviado:J. Biol. Chem.
ISSN:00219258
CODEN:JBCHA
CAS:cobalt, 7440-48-4; protoporphyrin, 553-12-8; Annexin A5; cobaltiprotoporphyrin, 14325-03-2; Culture Media, Serum-Free; DNA, 9007-49-2; Enzyme Inhibitors; Heme Oxygenase (Decyclizing), EC 1.14.99.3; Heme Oxygenase-1, EC 1.14.99.3; Heme, 14875-96-8; Luciferases, EC 1.13.12.-; Metalloporphyrins; Protoporphyrins; Receptors, G-Protein-Coupled; RNA, 63231-63-0; RNA, Messenger; tin protoporphyrin IX, 14325-05-4; Vascular Endothelial Growth Factor A
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_00219258_v281_n16_p11332_Marinissen.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v281_n16_p11332_Marinissen

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Citas:

---------- APA ----------
Marinissen, M.J., Tanos, T., Bolós, M., De Sagarra, M.R., Coso, O.A. & Cuadrado, A. (2006) . Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor. Journal of Biological Chemistry, 281(16), 11332-11346.
http://dx.doi.org/10.1074/jbc.M512199200
---------- CHICAGO ----------
Marinissen, M.J., Tanos, T., Bolós, M., De Sagarra, M.R., Coso, O.A., Cuadrado, A. "Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor" . Journal of Biological Chemistry 281, no. 16 (2006) : 11332-11346.
http://dx.doi.org/10.1074/jbc.M512199200
---------- MLA ----------
Marinissen, M.J., Tanos, T., Bolós, M., De Sagarra, M.R., Coso, O.A., Cuadrado, A. "Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor" . Journal of Biological Chemistry, vol. 281, no. 16, 2006, pp. 11332-11346.
http://dx.doi.org/10.1074/jbc.M512199200
---------- VANCOUVER ----------
Marinissen, M.J., Tanos, T., Bolós, M., De Sagarra, M.R., Coso, O.A., Cuadrado, A. Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor. J. Biol. Chem. 2006;281(16):11332-11346.
http://dx.doi.org/10.1074/jbc.M512199200