Focal adhesion kinase signaling in cardiac myocytes: new protein interactions and cell functions

• Grant number: 18/07383-6
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2019
• End date: October 31, 2022
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Aline Mara dos Santos
• Grantee: Aline Mara dos Santos
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Heart diseases are frequently associated with mass increase (hypertrophy) and alterations of shape and dimension of cardiac chambers (remodeling) as an adaptive response to mechanic and neurohumoral stimuli. Hypertrophy mainly results from an increase of cardiomyocytes area, while remodeling is characterized by cell death and fibrosis, which are determinant factors for cardiac failure. Among the signaling mechanisms that regulate the hypertrophy as well as the survival of cardiomyocytes, the signaling mediated by focal adhesion kinase (FAK) has been emerged as a key target, however, the molecular mechanisms regulated by FAK remain poorly studied. The objectives of this proposal are to identify new interaction partners for FAK and show the involvement of this kinase in several pathways related to the myocytes survival. Preliminary results indicate that FAK may regulate potential interactors, including enzymes that act on survival through the DNA damage response, such as PARP1, DNA-PK1, MRE11A, and XRCC5. Such interactions will be investigated on cardiac myocytes H9C2 and on rat left ventricle by a combination of functional and structural sophisticated techniques. The identification of the new FAK interaction partners and cellular functions regulated by these kinase, which could impact on the development of heart failure, continues to be a challenge. (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)

LIMA, MONICA FORCA; AMARAL, ALAN GONCALVES; MORETTO, ISABELA APARECIDA; PAIVA-SILVA, FRANCKSON JHONNE TORRES NEVES; PEREIRA, FLAVIA OLIVEIRA BORGES; BARBAS, CORAL; DOS SANTOS, ALINE MARA; SIMIONATO, ANA VALERIA COLNAGHI; RUPEREZ, FRANCISCO JAVIER. Untargeted Metabolomics Studies of H9c2 Cardiac Cells Submitted to Oxidative Stress, beta-Adrenergic Stimulation and Doxorubicin Treatment: Investigation of Cardiac Biomarkers. FRONTIERS IN MOLECULAR BIOSCIENCES, v. 9, p. 13-pg., 2022-06-29. (18/07383-6)

DA SILVA, MARIANA CONCEICAO; FABIANO, LILIAN CATARIM; DA COSTA SALOMAO, KARILE CRISTINA; DE FREITAS, PEDRO LUIZ ZONTA; NEVES, CAMILA QUAGLIO; BORGES, STEPHANIE CARVALHO; CARVALHO, MARIA DAS GRACAS DE SOUZA; BREITHAUPT-FALOPPA, ANA CRISTINA; DE THOMAZ, ANDRE ALEXANDRE; DOS SANTOS, ALINE MARA; et al. A Rodent Model of Human-Dose-Equivalent 5-Fluorouracil: Toxicity in the Liver, Kidneys, and Lungs. ANTIOXIDANTS, v. 12, n. 5, p. 21-pg., 2023-04-26. (18/07383-6, 20/11824-8)

AMARAL, ALAN GONCALVES; MORETTO, ISABELA APARECIDA; ZANDONADI, FLAVIA DA SILVA; ZAMORA-OBANDO, HANS ROLANDO; ROCHA, ISABELA; SUSSULINI, ALESSANDRA; DE THOMAZ, ANDRE ALEXANDRE; OLIVEIRA, REGINA VINCENZI; DOS SANTOS, ALINE MARA; SIMIONATO, ANA VALERIA COLNAGHI. Comprehending Cardiac Dysfunction by Oxidative Stress: Untargeted Metabolomics of In Vitro Samples. RONTIERS IN CHEMISTR, v. 10, p. 13-pg., 2022-04-08. (18/07383-6, 20/05965-8)