Addressing mechanistic questions on the induction process of cardiac hypertrophy mediated by the inflammation process: functional studies of CUGBP2 protein

• Grant number: 09/07671-2
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2009
• End date: January 31, 2012
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: Karen Cristiane Martinez de Moraes
• Grantee: Karen Cristiane Martinez de Moraes
• Host Institution: Instituto de Pesquisa e Desenvolvimento (IP&D). Universidade do Vale do Paraíba (UNIVAP). São José dos Campos , SP, Brazil

Abstract

Many factors can be pointed out as responsible elements for the development of cardiomyocyte hypertrophy. Accumulating evidence indicates an important role for inflamation in cardiac hypertrophy. This notion is based on the observation that in heart hypertrophic patients is found elevated plasma level of pro-inflatory cytokines. These cytokines have been implicated in the development of cardiac hypertrophy, most likely via downstream activation of pro-inflamatory transcription factors such as nuclear factor-kB (NF-kB), which is also responsible for the transcription of several different early genes, directly correlated with the hypertrophic heart condition. Besides, in the inflammatory process that leads to hypertrophy in cardiac cells, cyclooxygenase-2 (COX-2) has been found. COX-2 is an important enzyme usually expressed upon a cellular stimulli and it is involved in the control of prostaglandin pathway that plays major functions on the inflammatory cellular responses. Till now all the mechanistic details behind the cardiac hypertrophy and how COX-2 level is controlled in this process has not been completely elucidated. More recently evidence demonstrated a dynamic antagonism between COX-2 mRNA and the RNA-binding protein CUGBP2 in intestinal epitheilium that has been submitted to ionizing radiation. Based on this and in other CUGBP2 functions in a cell, this research proposal focus on the investigation of cellular and molecular mechanisms under the control of CUGBP2 in cardiomyocytes cell culture respectively treated with angiostensin II, phenylephrine, interleukin-1b and lipopolysaccharide as hypertrofic stimulators and NS398, a COX-2 inhibitor. Gene silencing, cellular assays, qRT-PCRs and Western blots will be performed in order to elucidate the major functions of CUGBP2 in cardiac hypertrophic processes. (AU)

Scientific publications

(4)

(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)

DA SILVA, BRENDA DE OLIVEIRA; ALBERICI, LUCIANE CARLA; RAMOS, LETICIA FERREIRA; SILVA, CAIO MATEUS; DA SILVEIRA, MARINA BONFOGO; DECHANT, CARLOS R. P.; FRIEDMAN, SCOTT L.; SAKANE, KUMIKO KOIBUCHI; GONCALVES, LETICIA ROCHA; MORAES, KAREN C. M.. Altered global microRNA expression in hepatic stellate cells LX-2 by angiotensin-(1-7) and miRNA-1914-5p identification as regulator of pro-fibrogenic elements and lipid metabolism. INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, v. 98, p. 137-155, MAY 2018. (09/07671-2, 13/21186-5, 10/17259-9)

DA SILVA, WALMIR; SOUZA DOS SANTOS, ROBSON AUGUSTO; MORAES, KAREN C. M.. Mir-351-5p contributes to the establishment of a pro-inflammatory environment in the H9c2 cell line by repressing PTEN expression. Molecular and Cellular Biochemistry, v. 411, n. 1-2, p. 363-371, JAN 2016. (09/07671-2)

MORAES, KAREN C. M.. RNA Surveillance: Molecular Approaches in Transcript Quality Control and their Implications in Clinical Diseases. Molecular Medicine, v. 16, n. 1-2, p. 53-68, JAN-FEB 2010. (09/07671-2)

MORAES, KAREN C. M.; MONTEIRO, CINTIA JUNIA; PACHECO-SOARES, CRISTINA. A novel function for CUGBP2 in controlling the pro-inflammatory stimulus in H9c2 cells: subcellular trafficking of messenger molecules. Cell Biology International, v. 37, n. 10, p. 1129-1138, OCT 2013. (09/07671-2)