Analysis of expression and activity of tetrahydrobiopterin enzymes pathway and tetrahydrobiopterin levels along melanoma development

• Grant number: 17/10695-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2017
• End date: July 31, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Fabiana Henriques Machado de Melo
• Grantee: Ricardo Coleto Xisto de Sousa
• Host Institution: Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP). Fundação Arnaldo Vieira de Carvalho. São Paulo , SP, Brazil

Abstract

The incidence of melanoma has been increasing in recent years due to increased life expectancy and increased exposure to ultraviolet rays. Melanoma is an extremely aggressive cancer, showing high rate of metastasis and consequently a high mortality. Late diagnosis, lack of tumor markers and inefficiency of available therapies are the main factors associated with high lethality. One of the mechanisms involved in the carcinogenesis of melanoma is the reactive oxygen species increase, among them the superoxide anion, which is produced by dysfunctional nitric oxide synthase (NOS). The superoxide anion activates signaling pathways associated with cell survival, increased proliferation and resistance to apoptosis, contributing to tumor development. The activity of NOS in endothelial cells is regulated by integrated mechanisms, including the bioavailability of the tetrahydrobiopterin cofactor (BH4). Data from our group show that NOS dysfunction due to decreased levels of BH4 contributes to the survival of metastatic melanoma cells, but other groups have shown that in other cancers, it is the increase in BH4 levels that favors carcinogenesis. Based on this information, the objective of this work is to evaluate at different stages of melanoma progression, the expression and activity of tetrahydrobiopterin enzymes synthesis and BH4 levels. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MACHADO DE MELO, FABIANA HENRIQUES; GONCALVES, DIEGO ASSIS; DE SOUSA, RICARDO XISTO; ICIMOTO, MARCELO YUDI; FERNANDES, DENISE DE CASTRO; LAURINDO, FRANCISCO R. M.; JASIULIONIS, MIRIAM GALVONAS. Metastatic Melanoma Progression Is Associated with Endothelial Nitric Oxide Synthase Uncoupling Induced by Loss of eNOS:BH4 Stoichiometry. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 17, SEP 2021. (14/13663-0, 17/10695-7, 17/04352-0)

MOURA SOARES, JAQUELINE PEREIRA; GONCALVES, DIEGO ASSIS; DE SOUSA, RICARDO XISTO; MOURO, MARGARETH GORI; HIGA, ELISA M. S.; SPERANDIO, LETICIA PAULINO; VITORIANO, CAROLINA MORAES; SANTA ROSA, ELISA BACHIR; DOS SANTOS, FERNANDA OLIVEIRA; DE QUEIROZ, GUSTAVO NERY; et al. Disruption of Redox Homeostasis by Alterations in Nitric Oxide Synthase Activity and Tetrahydrobiopterin along with Melanoma Progression. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 11, p. 20-pg., 2022-06-01. (17/04352-0, 21/12988-7, 17/10695-7, 21/04260-3, 19/27517-0)

GONCALVES, DIEGO ASSIS; XISTO, RICARDO; GONCALVES, JESSICA DOMINGUES; DA SILVA, DOUGLAS BACETI; MOURA SOARES, JAQUELINE PEREIRA; ICIMOTO, MARCELO YUDI; SANT'ANNA, CARLA; GIMENEZ, MARCELA; DE ANGELIS, RADA; LLESUY, SUSANA; et al. Imbalance between nitric oxide and superoxide anion induced by uncoupled nitric oxide synthase contributes to human melanoma development. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, v. 115, OCT 2019. (17/10695-7, 14/13663-0, 17/04352-0)