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The role of superoxide anion in the regulation of methionine cycle components during melanocyte malignant transformation

Grant number: 13/05946-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2013
Effective date (End): December 31, 2013
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Miriam Galvonas Jasiulionis
Grantee:Flávia Eichemberger Rius
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

In our laboratory a murine melanocyte malignant transformation model was developed when submitting a non- tumorigenic melanocyte cell line, melan-a cells, to a sequential cycles of anchorage blockade. Along melanoma progression alterations in epigenetic marks, homocysteine content and increased reactive oxygen species (ROS) levels was showed. We have shown that increased ROS regulates global DNA methylation pattern observed along malignant melanocyte transformation. DNA methylation is catalyzed by DNA methyltransfereases (DNMTs) using S-adenosylmethionine (SAM) as a methyl group donator. Homocysteine is a sulfur-containing aminoacid that can be metabolized via either transsulfuration or transmethylation pathways, being a key junction metabolite in methionine metabolism. Transsulfuration leads to glutathione biosynthesis, the major intracellular redox buffer of mammalian cells. In the transmethylation pathway the conversion of homocysteine to methionine is catalyzed by the B12-dependent zinc protein, methionine synthase and the conversion of methionine to SAM is catalysed by the enzyme methyl adenosil transferase. It was shown that increased ROS can regulate epigenetic marks through alterations in methionine components cycle in some disorders, including autism and lupus. Therefore, the aim of this work is to determine the levels of methionine cycle components in melanocytes subjected to anchorage blockade. (AU)