APVV-SK-FR-2015-0007

Effect of endoplasmic reticulum stress on ultrastructure and metabolism of mammalian cardiomyocytes

Principal Investigator: Marta Novotová

Duration: January 2016 – December 20173
Coordinating Organization: Institute of Molecular Physiology and Genetics SAS, Bratislava

Annotation:

Endoplasmic reticulum (ER) stress has been implicated in many cardiovascular diseases. Currently, the research on ER stress is aimed toward preservation of the beneficial adaptational response and elimination of the deleterious apoptosis in disease. The objective of this project is to study the adaptational changes in the cytoarchitecture of cardiomyocytes under ER stress, with focus on both, the smooth and rough forms of the reticular membrane system. We will characterize remodeling of myocyte cytoarchitecture induced by application of tunicamycine (the reticular stressor) in control mice and in mice with knocked-out sirtuin1 gene (SIRT1 ciKO mice). Sirtuin1 is a general metabolic energy sensor activated in response to cellular stress that protects cells from apoptosis. We hypothesize that SIRT1 may regulate the unfolded protein response and protect the heart against ER stress-induced damages.

Keywords:

Heart, muscle, reticular stress, cellular energatics, cytoarchitecture, ultrastructure, endoplasmic reticulum

Objectives:

Our proposed project, which builds on our previous collaboration, will focus on further study of the dynamics of the reticular membrane system of the mammalian heart muscle under conditions of reticular stress. The project involves two aspects: characterization of changes induced by reticular stress and studying the role of the protein sirtuin1 (SIRT1) in modulation of ER stress response in the cardiomyocytes. The first year will be devoted to the characterization of the morphology of the reticular membrane system of cardiomyocytes of murine papillary muscle under conditions of severe ER stress.

Publikácie:

	Pires Da Silva J, Monceaux K, Guilbert A, Gressette M, Piquereau J, Novotova M, Ventura-Clapier R, Garnier A, Lemaire C (2020): SIRT1 Protects the Heart from ER Stress-Induced Injury by Promoting eEF2K/eEF2-Dependent Autophagy. Cells. 9: E426 doi: 10.3390/cells9020426.
	Prola A, Nichtova Z, Pires Da Silva J, Piquereau J, Monceaux K, Guilbert A, Gressette M, Ventura-Clapier R, Garnier A, Zahradnik I, Novotova M, Lemaire C (2019): Endoplasmic reticulum stress induces cardiac dysfunction through architectural modifications and alteration of mitochondrial function in cardiomyocytes. Cardiovasc Res 115: 328-342, doi: 10.1093/cvr/cvy197.