Calcium and Reactive Oxygen Species Signaling Interplays in Cardiac Physiology and Pathologies

Abstract

Mitochondria are key players in energy production, critical activity for the smooth functioning of energy-demanding organs such as the muscles, brain, and heart. Therefore, dysregulation or alterations in mitochondrial bioenergetics primarily perturb these organs. Within the cell, mitochondria are the major site of reactive oxygen species (ROS) production through the activity of different enzymes since it is one of the organelles with the major availability of oxygen. ROS can act as signaling molecules in a number of different pathways by modulating calcium (Ca2+) signaling. Interactions among ROS and calcium signaling can be considered bidirectional, with ROS regulating cellular Ca2+ signaling, whereas Ca2+ signaling is essential for ROS production. In particular, we will discuss how alterations in the crosstalk between ROS and Ca2+ can lead to mitochondrial bioenergetics dysfunctions and the consequent damage to tissues at high energy demand, such as the heart. Changes in Ca2+ can induce mitochondrial alterations associated with reduced ATP production and increased production of ROS. These changes in Ca2+ levels and ROS generation completely paralyze cardiac contractility. Thus, ROS can hinder the excitation–contraction coupling, inducing arrhythmias, hypertrophy, apoptosis, or necrosis of cardiac cells. These interplays in the cardiovascular system are the focus of this review.

Cerium Oxide Nanoparticles Protect Cortical Astrocytes from Oxygen–Glucose Deprivation through Activation of the Ca2+ Signaling System

“…It is known that ROS production in cells is associated with and regulated by an increase in the concentration of cytosolic Ca 2+ ([Ca 2+ ] i ) [ 30 , 31 ]. Application of increasing concentrations of CeNPs to cortical astrocytes caused the generation of Ca 2+ signals even after application of 0.5 µg/mL nanoparticles.…”

The Na/K-ATPase α1/Src Signaling Axis Regulates Mitochondrial Metabolic Function and Redox Signaling in Human iPSC-Derived Cardiomyocytes

“…Physiological levels of ROS modulate key cell processes such as excitation-contraction coupling, cell differentiation, cell proliferation, and metabolic pathways [72,73]. In contrast, unbalanced ROS production can lead to oxidative stress commonly found in cardiovascular diseases [62][63][64][65][66]. CTS-induced NKA signaling can lead to ROS production, which perpetuates NKA signaling activation through a positive amplification loop [68,69].…”

“…Mammalian cells, including CM, have evolved strategies to regulate ROS levels to maintain physiological processes and survival. Low to moderate levels of ROS contribute to important functions, such as cell differentiation, growth, or apoptosis [62][63][64][65][66]. In contrast, a variety of pathological states, including cardiovascular disease, are associated with elevated ROS levels.…”

Mechanosensing by Piezo1 and its implications in the kidney

“…NF-kB has been shown to act as the upstream effector of NLRP3, thereby facilitating NLRP3 transcription and its assembly with ASC and pro-caspase 1. 185,186 Activation of Piezo1 channels triggers Ca 2+ influx, signaling pathways involved in remodeling of Ca 2+ handling include those mediated by reactive oxygen species (ROS), CaMKII or PI3K-Akt, etc 96,187,188 (Figure 4C). These pathways enable to directly/ indirectly involved in chronic Inflammation in other tissues (although not reported in the kidney), such as activating the NF-kB.…”