دورية أكاديمية
Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor
| العنوان: | Inhibition of heme oxygenase-1 interferes with the transforming activity of the Kaposi sarcoma herpesvirus-encoded G protein-coupled receptor |
|---|---|
| المؤلفون: | Marinissen, M.J., Tanos, T., Bolós, M., De Sagarra, M.R., Coso, O.A., Cuadrado, A. |
| المصدر: | J. Biol. Chem. 2006;281(16):11332-11346 |
| سنة النشر: | 2006 |
| المجموعة: | Repositorio Digital Institucional - Universidad de Buenos Aires (RDI UBA) |
| مصطلحات موضوعية: | 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, genetic transfection, Human herpesvirus 8, mouse, nonhuman, priority journal, protein expression, Animals |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| العلاقة: | http://hdl.handle.net/20.500.12110/paper_00219258_v281_n16_p11332_MarinissenTest; http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_00219258_v281_n16_p11332_Marinissen_oaiTest |
| الإتاحة: | https://doi.org/20.500.12110/paper_00219258_v281_n16_p11332_MarinissenTest https://hdl.handle.net/20.500.12110/paper_00219258_v281_n16_p11332_MarinissenTest http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_00219258_v281_n16_p11332_Marinissen_oaiTest |
| حقوق: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/2.5/arTest |
| رقم الانضمام: | edsbas.3F35905C |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |