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Gene-diet interaction in mice supplemented with methionine in the fetal and postnatal periods: studies of genomic instability, methylation and expression of genes related to cardiovascular diseases

Grant number: 10/01410-0
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): May 01, 2010
Effective date (End): January 31, 2014
Field of knowledge:Health Sciences - Nutrition - Nutrition Biochemistry
Principal Investigator:Lusânia Maria Greggi Antunes
Grantee:Alexandre Ferro Aissa
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):12/10872-2 - MicroRNA expression analysis in female mice treated with methionine-deficient or -supplemented diets during pregnancy, BE.EP.DR

Abstract

Epigenetics can be defined as the study of heritable changes of a phenotype such as gene expression patterns that are not caused by changes in the nucleotide sequence or the genetic code. Among the most studied epigenetic mechanism is DNA methylation. This process is the addition of a methyl at carbon number five of the aromatic ring of cytosine, to form the basis methylcytosine. Mammalian one carbon metabolism provides the methyl group for all methylation reactions. These are dependent on methyl donors. Methionine obtained from the diet is a major donor of methyl groups to cytosine. Methylation occurs predominantly in CpG dinucleotides. In mammalian genomes the distribution of CpG sequences is mainly located in regions called CpG islands and are commonly found in promoter regions of genes participating in regulation of gene transcription. During the reproductive process, the genome of mammals undergoes a profound reprogramming of methylation patterns in germ cells and in the early stages of pre-implantation embryo. Therefore, disruption of the methylation pathway may cause epigenetic defects during the embryonic period and favor the emergence of diseases throughout the life of the individual. Studies suggest that one of the mechanisms that are most influenced in this period, due to lack of nutrients such as methionine, is the process of DNA methylation. It is also known that problems in DNA methylation affect the expression of genes linked to the emergence of cardiovascular disease. Therefore, this study aims to assess whether the ACE, APOA5, PPARg, MTHFR genes are subject to change of expression and the methylation pattern influenced by a methionine-supplemented diet or a methionine-deficient diet during pregnancy, in female mice and their offspring.

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Scientific publications (5)
(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)
AISSA, ALEXANDRE FERRO; TRYNDYAK, VOLODYMYR P.; DE CONTI, ALINE; THOMAZELA MACHADO, ANA RITA; TUTTIS, KATIUSKA; MACHADO, CARLA DA SILVA; HERNANDES, LIVIA CRISTINA; DA SILVA SANTOS, PATRICK WELLINGTON; SERPELONI, JULIANA MARA; POGRIBNY, IGOR P.; et al. Epigenetic changes induced in mice liver by methionine-supplemented and methionine-deficient diets. Food and Chemical Toxicology, v. 163, p. 10-pg., . (10/01410-0, 13/02365-6)
AISSA, ALEXANDRE FERRO; DO AMARAL, CATIA LIRA; VENANCIO, VINICIUS PAULA; MACHADO, CARLA DA SILVA; HERNANDES, LIVIA CRISTINA; DA SILVA SANTOS, PATRICK WELLINGTON; CURI, RUI; PIRES BIANCHI, MARIA DE LOURDES; GREGGI ANTUNES, LUSANIA MARIA. Methionine-supplemented diet affects the expression of cardiovascular disease-related genes and increases inflammatory cytokines in mice heart and liver. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES, v. 80, n. 19-21, SI, p. 1116-1128, . (13/02365-6, 10/01410-0)
AISSA, ALEXANDRE FERRO; URSULA HERMOGENES GOMES, TARSILA DAYSY; ALMEIDA, MARA RIBEIRO; HERNANDES, LIVIA CRISTINA; CASTANIA DARIN, JOANA D'ARC; PIRES BIANCHI, MARIA LOURDES; GREGGI ANTUNES, LUSANIA MARIA. Methionine concentration in the diet has a tissue-specific effect on chromosomal stability in female mice. Food and Chemical Toxicology, v. 62, p. 456-462, . (13/02365-6, 10/01410-0)
AISSA, ALEXANDRE FERRO; DO AMARAL, CATIA LIRA; VENANCIO, VINICIUS PAULA; MACHADO, CARLA DA SILVA; HERNANDES, LIVIA CRISTINA; DA SILVA SANTOS, PATRICK WELLINGTON; CURI, RUI; PIRES BIANCHI, MARIA DE LOURDES; GREGGI ANTUNES, LUSANIA MARIA. Methionine-supplemented diet affects the expression of cardiovascular disease-related genes and increases inflammatory cytokines in mice heart and liver. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES, v. 80, n. 19-21, p. 13-pg., . (13/02365-6, 10/01410-0)
AISSA, ALEXANDRE FERRO; TRYNDYAK, VOLODYMYR; DE CONTI, ALINE; MELNYK, STEPAN; URSULA HERMOGENES GOMES, TARSILA DAYSY; PIRES BIANCHI, MARIA LOURDES; JAMES, S. JILL; BELAND, FREDERICK A.; GREGGI ANTUNES, LUSANIA MARIA; POGRIBNY, IGOR P.. Effect of methionine-deficient and methionine-supplemented diets on the hepatic one-carbon and lipid metabolism in mice. MOLECULAR NUTRITION & FOOD RESEARCH, v. 58, n. 7, p. 1502-1512, . (10/01410-0, 12/10872-2)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
AISSA, Alexandre Ferro. Gene-diet interaction in mice supplemented with methionine in the fetal and postnatal periods: studies of genomic instability, methylation and expression of genes related to cardiovascular diseases. 2014. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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