Imbalance between nitric oxide and superoxide anion induced by uncoupled nitric oxide synthase contributes to human melanoma development

Autor(es):Mostrar menos -

Goncalves, Diego Assis ^{[1, 2]} ; Xisto, Ricardo ^[3] ; Goncalves, Jessica Domingues ^[1] ; da Silva, Douglas Baceti ^[3] ; Moura Soares, Jaqueline Pereira ^[3] ; Icimoto, Marcelo Yudi ^[4] ; Sant'Anna, Carla ^[3] ; Gimenez, Marcela ^[3] ; de Angelis, Rada ^[3] ; Llesuy, Susana ^[5] ; Fernandes, Denise C. ^[6] ; Laurindo, Francisco ^[6] ; Jasiulionis, Miriam Galvonas ^[1] ; Machado de Melo, Fabiana Henriques ^[3]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Pharmacol Dept, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Microimunoparasitol, Sao Paulo - Brazil

^[3] Santa Casa Sao Paulo Sch Med Sci, Dept Physiol Sci, Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Biophys Dept, Sao Paulo - Brazil

^[5] Univ Buenos Aires, Dept Gen & Inorgan Chem, Buenos Aires, DF - Argentina

^[6] Univ Sao Paulo Sch Med, Heart Inst InCor, Vasc Biol Lab, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY; v. 115, OCT 2019.
• Citações Web of Science: 1

Resumo

Melanoma is the most aggressive type of cutaneous tumors due to its metastatic potential and high mortality. Increased levels of reactive oxygen species, including superoxide anion (O-2(center dot-)), and the consequent installation of a pro-oxidant environment are associated with melanoma development. The enzyme nitric oxide synthase (NOS), responsible for the production of nitric oxide (NO), when uncoupled is as a source of O-2(center dot-), for example by the absence of its cofactor tetrahydrobiopterin (BH4). Western blot analysis showed increased expression of endothelial and inducible NOS in human melanoma cells, altering the stoichiometry between NOS levels and BH4 concentration and together with decreased BH4:BH2 ratio are contributing to NOS uncoupling. The treatment of melanoma cells with exogenous BH4 increased NO concentration and decreased O-2(center dot-) levels, leading to NOS coupling, which in turn reduced cell viability, cell proliferation and the ability of melanoma cells to form melanoma spheroids. Moreover, BH4 level restoration rendered melanoma cells more sensitive to apoptosis, demonstrating the role of dysfunctional NOS in melanoma genesis. (AU)

• Processo FAPESP: 17/10695-7 - Avaliação da expressão e atividade das enzimas que participam da síntese da tetrahidrobiopterina e dos níveis de tetrahidrobipterina ao longo da gênese do melanoma
• Beneficiário: Ricardo Coleto Xisto de Sousa
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 14/13663-0 - Integração de dados de expressão de genes e microRNAs, metiloma e hidroximetiloma de diferentes etapas da progressão do melanoma.
• Beneficiário: Miriam Galvonas Jasiulionis
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/04352-0 - Contribuição da interação entre a caveolina-1 e as enzimas GTP ciclohidrolase I e sintase de óxido nítrico ao longo da progressão do melanoma
• Beneficiário: Fabiana Henriques Machado de Melo
• Modalidade de apoio: Auxílio à Pesquisa - Regular