| Endothelial nitric oxide synthase uncoupling as a key mediator for melanocyte malignant transformation associated with sustained stress condition. | |
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MedLine Citation:
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PMID: 21362470 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Melanoma cell lines and cells corresponding to pre-malignant melanocytes were established by our group after submitting a non-tumorigenic murine melanocyte lineage, melan-a, to sequential cycles of anchorage blockade. Previous results showed that in melan-a cells superoxide level increases after such procedure. Superoxide production during melanocyte de-adhesion was inhibited by L-sepiapterin, precursor of eNOS cofactor BH4, and increased with inhibitor of BH4 synthesis, DAHP, hence indicating a partial uncoupling state of eNOS. The eNOS uncoupling seems to be maintained in cells derived from melan-a, since they present decreased nitric oxide and increased superoxide levels. The inhibition of superoxide production in Tm5 melanoma cells with L-sepiapterin reinforces their eNOS uncoupled state. The maintenance of oxidative stress seems to be important in melanoma apoptosis resistance since Mn(III)TBAP, a superoxide scavenger, or L-sepiapterin render Tm5 cells more sensitive to anoikis and chemotherapy. More importantly, eNOS uncoupling seems to exert a pivoltal role in melanocyte malignant transformation induced by sustained anchorage impediment, since no malignant transformation was observed when L-NAME-treated melanocytes were submitted to sequential cycles of de-adhesion. Our results show that uncoupled eNOS contribute to superoxide production during melanocyte anchorage impediment, contributing to anoikis resistance and malignant transformation. |
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Authors:
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Fabiana H M Melo; Fernanda Molognoni; Alice S Morais; Mariana Toricelli; Margareth G Mouro; Elisa M S Higa; José D Lopes; Miriam G Jasiulionis |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-2-26 |
Journal Detail:
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Title: Free radical biology & medicine Volume: - ISSN: 1873-4596 ISO Abbreviation: - Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-3-2 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2010. Published by Elsevier Inc. |
Affiliation:
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Disciplina de Imunologia, Universidade Federal de São Paulo, UNIFESP. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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