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Title: Imbalance between nitric oxide and superoxide anion induced by uncoupled nitric oxide synthase contributes to human melanoma development
Authors: GONCALVES, Diego AssisXISTO, RicardoGONCALVES, Jessica DominguesSILVA, Douglas Baceti daSOARES, Jaqueline Pereira MouraICIMOTO, Marcelo YudiSANT'ANNA, CarlaGIMENEZ, MarcelaANGELIS, Rada deLLESUY, SusanaFERNANDES, Denise C.LAURINDO, FranciscoJASIULIONIS, Miriam GalvonasMELO, Fabiana Henriques Machado de
Citation: INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, v.115, article ID UNSP 105592, 11p, 2019
Abstract: 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.
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Artigos e Materiais de Revistas Científicas - HC/InCor
Instituto do Coração - HC/InCor

Artigos e Materiais de Revistas Científicas - LIM/64
LIM/64 - Laboratório de Investigação Médica em Biologia Cardiovascular Translacional

Artigos e Materiais de Revistas Científicas - ODS/03
ODS/03 - Saúde e bem-estar

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