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EVALUATION EPIGENETIC MECHANISM BY DNA METHYLATION AND EXPRESSION OF GLUT4 AND IRS-1 IN SKELETAL MUSCLE TISSUE OF ADULT RATS, OFFSPRING OF RATS WITH PERIODONTAL DISEASE

Grant number: 15/12018-7
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2016
Effective date (End): August 15, 2019
Field of knowledge:Health Sciences - Dentistry - Social and Preventive Dentistry
Principal Investigator:Doris Hissako Sumida
Grantee:Maria Sara de Lima Coutinho Mattera
Home Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
Associated scholarship(s):17/13817-6 - CERAMIDE PRODUCES VASCULAR DYSFUNCTION VIA AUTONOMOUS ACTIONS WITHIN THE ENDOTHELIUM, BE.EP.DR

Abstract

The fetal programming hypothesis suggests that intrauterine stimuli or aggression can induce metabolic and physiology changes in offspring, increasing the diseases risk in adulthood. Permanent changes in DNA methylation and gene expression are considered molecular mechanisms responsible for this programming. Previous studies have shown that maternal periodontal disease (PD) promotes insulin resistance, increased in the plasma concentrations of cytokines, decrease in GLUT4 content in the plasma membrane and its translocation index in their adult offspring. Cytokines such as TNF-a have been associated with reduced GLUT4 expression.Moreover, this cytokine may stimulate some serine kinases including IkB kinase (IKK) and c-Jun N-terminal kinase (JNK) that promote IRS-1 phosphorylation on serine residues, resulting in attenuation of the insulin signal. These findings reveal the need for more studies to verify the mechanisms involved in these changes. Therefore, the objectives of the present study will be evaluate in adult rats, offspring of rats with periodontal disease: 1)plasma concentrations of glucose and insulin; 2) mRNA expression of the glucose transporter protein 4 (GLUT4) and IRS-1; 3) the degree of DNA methylation in the promoter region of gene of GLUT4 and IRS-1;4) phosphorylation of JNK and IKKB proteins and their total contents in gastrocnemius skeletal muscle tissue (GM).The rats will be distributed into two groups: 1) with periodontal disease (PED), in which the disease is induced by ligation with silk thread around the 1st molar, 2) control rats (CN). Seven days after ligature placement, the rats of both groups will be placed for mating, verifying daily by vaginal smear, the day of copulation. Pregnant rats will be separated into individual boxes. When male offspring of these rats completed 75 days, will be performing the experiments: 1)plasma concentrations of glucose and insulin; 2) mRNA expression of GLUT4 and IRS-1; 3) the degree of DNA methylation in the promoter region of gene of GLUT4 and IRS-1;4) phosphorylation of JNK and IKKB proteins and their total contents in GM. Statistical analysis will be done by T Student method for unpaired samples, and the differences between the two groups will be considered significant when p <0.05.

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)
DE LIMA COUTINHO MATTERA, MARIA SARA; CHIBA, FERNANDO YAMAMOTO; LOPES, FLAVIA LOMBARDI; SAORI TSOSURA, THAIS VERONICA; PERES, MARIA ANGELICA; BALERA BRITO, VICTOR GUSTAVO; PENHA DE OLIVEIRA, SANDRA HELENA; PEREIRA, RENATO FELIPE; MARANI, FERNANDO; DOS SANTOS, RODRIGO MARTINS; BELARDI, BIANCA ELVIRA; LATTARI TESSARIN, GESTTER WILLIAN; BENITES, MARIANA LOPES; ERVOLINO, EDILSON; HEIMANN, JOEL CLAUDIO; SUMIDA, DORIS HISSAKO. Effect of maternal periodontitis on GLUT4 and inflammatory pathway in adult offspring. Journal of Periodontology, v. 90, n. 8, p. 884-893, AUG 2019. Web of Science Citations: 0.
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
MATTERA, Maria Sara de Lima Coutinho. Avaliação do mecanismo epigenético por metilação do DNA e da expressão de GLUT4 em tecido muscular esquelético de ratos adultos, proles de ratas com doença periodontal. 2019. 84 f. Doctoral Thesis - Universidade Estadual Paulista (Unesp) Faculdade de Odontologia.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.