Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor

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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-i...

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Autores principales:	Marinissen, M.J., Tanos, T., Bolós, M., De Sagarra, M.R., Coso, O.A., Cuadrado, A.
Formato:	Artículo publishedVersion
Lenguaje:	Inglés
Publicado:	2006
Materias:	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, Messenger Time Factors Transfection Up-Regulation Vascular Endothelial Growth Factor A Herpesviridae Mus musculus
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00219258_v281_n16_p11332_Marinissen
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paperaa:paper_00219258_v281_n16_p11332_Marinissen2023-06-12T16:42:55Z 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 Marinissen, M.J. Tanos, T. Bolós, M. De Sagarra, M.R. Coso, O.A. Cuadrado, A. 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 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. Fil:Tanos, T. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Coso, O.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2006 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00219258_v281_n16_p11332_Marinissen
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
language	Inglés
orig_language_str_mv	eng
topic	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
spellingShingle	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 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
topic_facet	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
description	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.
format	Artículo Artículo publishedVersion
author	Marinissen, M.J. Tanos, T. Bolós, M. De Sagarra, M.R. Coso, O.A. Cuadrado, A.
author_facet	Marinissen, M.J. Tanos, T. Bolós, M. De Sagarra, M.R. Coso, O.A. Cuadrado, A.
author_sort	Marinissen, M.J.
title	Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor
title_short	Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor
title_full	Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor
title_fullStr	Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor
title_full_unstemmed	Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor
title_sort	inhibition of heme oxygenase-1 interferes with the transforming activity of the kaposi sarcoma herpesvirus-encoded g protein-coupled receptor
publishDate	2006
url	http://hdl.handle.net/20.500.12110/paper_00219258_v281_n16_p11332_Marinissen
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Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor

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