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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
Melo, Fabiana H. M. [1] ; Molognoni, Fernanda [2, 1] ; Morais, Alice S. [2] ; Toricelli, Mariana [2] ; Mouro, Margareth G. [3] ; Higa, Elisa M. S. [3] ; Lopes, Jose D. [1] ; Jasiulionis, Miriam G. [1, 2]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Fed Sao Paulo, Disciplina Imunol, BR-04023900 Sao Paulo - Brazil
[2] Univ Fed Sao Paulo, Disciplina Farmacol, BR-04023900 Sao Paulo - Brazil
[3] Univ Fed Sao Paulo, Disciplina Nefrol, BR-04023900 Sao Paulo - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Free Radical Biology and Medicine; v. 50, n. 10, p. 1263-1273, MAY 15 2011.
Citações Web of Science: 10
Resumo

Melanoma 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. (AU)

Processo FAPESP: 06/61293-1 - Contribuição da metilação de DNA na carcinogênese
Beneficiário:Miriam Galvonas Jasiulionis
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
Processo FAPESP: 05/60334-3 - Contribuição do ânion superóxidos e do óxido nítrico na transformação maligna de melanócitos
Beneficiário:Fabiana Henriques Machado de Melo
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 09/03335-8 - Identificação de genes que apresentam expressão alterada devido à metilação aberrante de seu promotor nas fases iniciais da progressão do melanoma
Beneficiário:Alice Santana Morais
Linha de fomento: Bolsas no Brasil - Mestrado