VEGA 2/0110/15

The effect of myocardial load on distribution of the endoplasmic membrane reticulum of cardiac myocytes

Principal Investigator: Marta Novotová

Duration: January 2015 – December 2017
Coordinating Organization: Institute of Molecular Physiology and Genetics SAS, Bratislava

Annotation:

Cardiac muscle is capable of flexible adaptation to physiological demands of an organism that, however, fails under pathophysiological load. The underlying mechanisms are not understood at the level of cardiac myocytes. The aim of this project is to characterize the response of the endo/sarcoplasmic reticular membrane system of cardiac myocytes to physiological and pathophysiological load. Methods of electron and confocal fluorescence microscopy will be employed to study the distribution of morphologically different domains of smooth and rough reticular network (perinuclear, perimyofibrilar, and perimitochondrial) of left ventricular and papillary muscles of rat myocardium. By means of quantitative stereological analysis of random images of random tissue samples we will estimate changes in the content and environment of individual reticular domains. The measured data will allow us to elucidate the consequences of endo-reticular membrane remodelling on calcium signalling and metabolism of myocytes.

Keywords:

Cardiac myocytes, remodelling, reticulum, electron microscopy, morphology, stereological analysis

Objectives:

The main goal of the project is to find out how the mammalian endo-membrane system (ER/SR) participates on remodeling of myocyte structure to changed myocardial load. We will measure changes in volume density, surface density and nearest environment of the smooth and rough reticular system in three functionally different albeit mutually related domains of myocyte – perimyofibrilar, perimitochondrial and perinuclear. The data acquired in this project will allow to identify and characterize specific reactions of functionally specialized domains and forms of reticular membranes and to determine their contribution to myocyte adaptation to variable loads.

Comparison of the ranges and patterns of the reactions of smooth and rough forms of the reticular system with the reactions of the contractile, energetic and proteosynthetic domains of myocytes will allow to identify impairment in the proportionality of development within and between function-specific domains of myocytes.

Publications:

	Piquereau J, Veksler V, Novotova M, Ventura-Clapier R (2020): Energetic interactions between subcellular organelles in striated muscles. Front Cell Dev Biol 8: 581045 doi: 10.3389/fcell.2020.581045.
	Novotova M, Zahradnikova A Jr, Nichtova Z, Kovac R, Kralova E, Stankovicova T, Zahradnikova A, Zahradnik I (2020): Structural variability of dyads relates to calcium release in rat ventricular myocytes. Sci Rep 10: 8076 doi: 10.1038/s41598-020-64840-5.
	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.
	Ragni CV, Diguet N, Le Garrec JF, Novotova M, Resende TP, Pop S, Charon N, Guillemot L, Kitasato L, Badouel C, Dufour A, Olivo-Marin JC, Trouvé A, McNeill H, Meilhac SM. (2017): Amotl1 mediates sequestration of the Hippo effector Yap1 downstream of Fat4 to restrict heart growth. Nat Commun 27: 14582.
	Misuth M, Joniova J, Horvath D, Dzurova L, Nichtova Z, Novotova M, Miskovsky P, Stroffekova K, Huntosova V. (2017): The flashlights on a distinct role of protein kinase C δ: Phosphorylation of regulatory and catalytic domain upon oxidative stress in glioma cells. Cell Signal 34: 11–22.
	Huntosova V, Novotova M, Nichtova Z, Balogova L, Maslanakova M, Petrovajova D, Stroffekova K (2017): Assessing light-independent effects of hypericin on cell viability, ultrastructure and metabolism in human glioma and endothelial cells. Toxicol In Vitro 40: 184–195.
	Novotova M, Tarabova B, Tylkova L, Ventura-Clapier R, Zahradnik I (2016): Ultrastructural remodelling of slow skeletal muscle fibres in creatine kinase deficient mice: a quantitative study. Gen Physiol Biophys 35: 477–486.