Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor
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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Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v281_n16_p11332_Marinissen http://hdl.handle.net/20.500.12110/paper_00219258_v281_n16_p11332_Marinissen |
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paper:paper_00219258_v281_n16_p11332_Marinissen2023-06-08T14:43:27Z Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor Tanos, Tamara Coso, Omar Adrian 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 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v281_n16_p11332_Marinissen 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) |
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 Tanos, Tamara Coso, Omar Adrian 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. |
author |
Tanos, Tamara Coso, Omar Adrian |
author_facet |
Tanos, Tamara Coso, Omar Adrian |
author_sort |
Tanos, Tamara |
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 |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00219258_v281_n16_p11332_Marinissen http://hdl.handle.net/20.500.12110/paper_00219258_v281_n16_p11332_Marinissen |
work_keys_str_mv |
AT tanostamara inhibitionofhemeoxygenase1interfereswiththetransformingactivityofthekaposisarcomaherpesvirusencodedgproteincoupledreceptor AT cosoomaradrian inhibitionofhemeoxygenase1interfereswiththetransformingactivityofthekaposisarcomaherpesvirusencodedgproteincoupledreceptor |
_version_ |
1768546477180715008 |