The Oxidative Balance Orchestrates the Main Keystones of the Functional Activity of Cardiomyocytes

Abstract

This review is aimed at providing an overview of the key hallmarks of cardiomyocytes in physiological and pathological conditions. The main feature of cardiac tissue is the force generation through contraction. This process requires a conspicuous energy demand and therefore an active metabolism. The cardiac tissue is rich of mitochondria, the powerhouses in cells. These organelles, producing ATP, are also the main sources of ROS whose altered handling can cause their accumulation and therefore triggers detrimental effects on mitochondria themselves and other cell components thus leading to apoptosis and cardiac diseases. This review highlights the metabolic aspects of cardiomyocytes and wanders through the main systems of these cells: (a) the unique structural organization (such as different protein complexes represented by contractile, regulatory, and structural proteins); (b) the homeostasis of intracellular Ca2+ that represents a crucial ion for cardiac functions and E-C coupling; and (c) the balance of Zn2+, an ion with a crucial impact on the cardiovascular system. Although each system seems to be independent and finely controlled, the contractile proteins, intracellular Ca2+ homeostasis, and intracellular Zn2+ signals are strongly linked to each other by the intracellular ROS management in a fascinating way to form a “functional tetrad” which ensures the proper functioning of the myocardium. Nevertheless, if ROS balance is not properly handled, one or more of these components could be altered resulting in deleterious effects leading to an unbalance of this “tetrad” and promoting cardiovascular diseases. In conclusion, this “functional tetrad” is proposed as a complex network that communicates continuously in the cardiomyocytes and can drive the switch from physiological to pathological conditions in the heart.

P4HA2‐mediated HIF‐1α stabilization promotes erdafitinib‐resistance in FGFR3‐alteration bladder cancer

“…Then by interfering with lysosomes, Erdafitinib blocked autolysosome degradation. Blocked autolysosome degradation resulted in blocked autophagy, through which Erdafitinib elevated intracellular ROS level, causing DNA damage accumulation and apoptosis, which is consistent with previous literature 31,32 …”

“…While a low level of ROS activates the signaling pathways required for tumor cell proliferation, survival and metastasis, [33][34][35] high level of ROS leads to DNA damage and induces apoptosis. 31,32 HIF-1 is a key regulator of ROS. Activation of the HIF-1 pathway induces glycolysis gene expression and inhibits oxidative phosphorylation.…”

“…Blocked autolysosome degradation resulted in blocked autophagy, through which Erdafitinib elevated intracellular ROS level, causing DNA damage accumulation and apoptosis, which is consistent with previous literature. 31,32 Abnormal metabolism of ROS is one of the characteristics of tumor cells. ROS have dual roles in the regulation of tumor cells.…”

“…ROS have dual roles in the regulation of tumor cells. While a low level of ROS activates the signaling pathways required for tumor cell proliferation, survival and metastasis, 33–35 high level of ROS leads to DNA damage and induces apoptosis 31,32 . HIF‐1 is a key regulator of ROS.…”

The role of endosarcomeric cytoskeleton proteins in the mechanisms of left ventricular diastolic dysfunction: focus on titin

“…Нарушение фосфорилирования отдельных частей молекулы титина или активацию под влиянием некоторых факторов (например, шаперона Hsp90, индукторов и продуктов окислительного стресса или провоспалительных цитокинов) ее дефосфорилирования серин/треонин фосфатазой 5 относят к титин-зависимым механизмам развития повышения жесткости миокарда и диастолической сердечной недостаточности [12,49,53,54,[95][96][97][98]. Поскольку дифференцированные сегменты отдельных изоформ титина в растяжимой части I-полосы могут фосфорилироваться различными протеинкиназами, что приводит к неодинаковым эффектам, выяснение статуса фосфорилирования титина важно, когда требуется всестороннее понимание механизмов изменения жесткости миокарда при развитии сердечной недостаточности с сохраненной ФВ ЛЖ [80,99].…”