Endothelial nitric oxide synthase uncoupling as a key mediator of melanocyte malignant transformation associated with sustained stress conditions

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dc.contributor.authorMelo, Fabiana Henriques Machado de [UNIFESP]
dc.contributor.authorMolognoni, Fernanda [UNIFESP]
dc.contributor.authorMorais, Alice Santana [UNIFESP]
dc.contributor.authorToricelli, Mariana [UNIFESP]
dc.contributor.authorMouro, Margaret Gori [UNIFESP]
dc.contributor.authorHiga, Elisa Mieko Suemitsu [UNIFESP]
dc.contributor.authorLopes, Jose Daniel [UNIFESP]
dc.contributor.authorJasiulionis, Miriam Galvonas [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:16:45Z
dc.date.available2016-01-24T14:16:45Z
dc.date.issued2011-05-15
dc.description.abstractMelanoma cell lines and cells corresponding to premalignant melanocytes were established by our group after subjecting a nontumorigenic murine melanocyte lineage, melan-a, to sequential cycles of anchorage blockade. Previous results showed that in melan-a cells the superoxide level increases after such procedure. Superoxide production during melanocyte de-adhesion was inhibited by L-sepiapterin, the precursor of eNOS cofactor BH(4), and increased by the inhibitor of BH(4) synthesis, DAHP, hence indicating a partial uncoupling state of eNOS. the eNOS uncoupling seems to be maintained in cells derived from melan-a, because 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 because Mn(III)TBAP, a superoxide scavenger, or L-sepiapterin renders Tm5 cells more sensitive to anoikis and chemotherapy. More importantly, eNOS uncoupling seems to play a pivotal role in melanocyte malignant transformation induced by sustained anchorage impediment, because no malignant transformation was observed when L-NAME-treated melanocytes were subjected to sequential cycles of de-adhesion. Our results show that uncoupled eNOS contributes to superoxide production during melanocyte anchorage impediment, contributing to anoikis resistance and malignant transformation. (C) 2011 Elsevier Inc. All rights reserved.en
dc.description.affiliationUniversidade Federal de São Paulo, Disciplina Imunol, BR-04023900 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Disciplina Farmacol, BR-04023900 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Disciplina Nefrol, BR-04023900 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Disciplina Imunol, BR-04023900 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Disciplina Farmacol, BR-04023900 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Disciplina Nefrol, BR-04023900 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipIDFAPESP: 06/61293-1
dc.description.sponsorshipIDFAPESP: 05/60334-3
dc.description.sponsorshipIDFAPESP: 08/50366
dc.description.sponsorshipIDFAPESP: 09/03335-8
dc.format.extent1263-1273
dc.identifierhttp://dx.doi.org/10.1016/j.freeradbiomed.2011.02.022
dc.identifier.citationFree Radical Biology and Medicine. New York: Elsevier B.V., v. 50, n. 10, p. 1263-1273, 2011.
dc.identifier.doi10.1016/j.freeradbiomed.2011.02.022
dc.identifier.fileWOS000290694900007.pdf
dc.identifier.issn0891-5849
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/33702
dc.identifier.wosWOS:000290694900007
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofFree Radical Biology and Medicine
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjecteNOS uncouplingen
dc.subjectSuperoxide anionen
dc.subjectMelanocytesen
dc.subjectAnoikisen
dc.subjectMalignant transformationen
dc.subjectFree radicalsen
dc.titleEndothelial nitric oxide synthase uncoupling as a key mediator of melanocyte malignant transformation associated with sustained stress conditionsen
dc.typeinfo:eu-repo/semantics/article
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