Oxygen free radicals and calcium homeostasis in the heart

Abstract

Many experiments have been done to clarify the effects of oxygen free radicals on Ca 2+ homeostasis in the hearts. A burst of oxygen free radicals occurs immediately after reperfusion, but we have to be reminded that the exact levels of oxygen free radicals in the hearts are yet unknown in both physiological and pathophysiological conditions. Therefore, we should give careful consideration to this point when we perform the experiments and analyze the results.It is, however, evident that Ca 2+ overload occurs when the hearts are exposed to an excess amount of oxygen free radicals. Though ATP-independent Ca 2+ binding is increased, Ca 2+ influx through Ca 2 § channel does not increase in the presence of oxygen free radicals. Another possible pathway through which Ca 2. can enter the myocytes is Na+-Ca 2+ exchanger. Although, the activities ofNa § + ATPase and Na+-H + exchange are inhibited by oxygen free radicals, it is not known whether intracellular Na § level increases under oxidative stress or not. The question has to be solved for the understanding of the importance of Na § Ca z+ exchange in Ca 2+ influx process from extracellular space. Another question is 'which way does Na+-Ca 2+ exchange work under oxidative stress? Net influx or efflux of Ca 2 § ?' Membrane permeability for Ca 2+ may be maintained in a relatively early phase of free radical injury. Since sarcolemmal Ca2+-pumpATPase activity is depressed by oxygen free radicals, Ca 2 § extrusion from cytosol to extracellular space is considered to be reduced. It has also been shown that oxygen free radicals promote Ca 2 § release from sarcoplasmic reticulum and inhibit Ca 2+ sequestration to sarcoplasmic reticulum. Thus, these changes in Ca 2+ handling systems could cause the Ca 2+ overload due to oxygen free radicals. (Mol Cell Biochem 139: 91-100, 1994)

Cloning, expression and characterization of the ornithine decarboxylase gene from Dictyostelium discoideum

“…In addition, elevation of cytoplasmic Ca 2+ can lead to production of reactive oxygen species and vice-versa (Minois et al, 2011). Oxidative stress could disrupt calcium homeostasis by promoting membrane lipid peroxidation and covalent modification of transporters (Jain and Shohet 1981;Kaneko et al, 1994). Both oxidative stress and disruption of Ca 2+ homeostasis appear to contribute to autophagy (Swer et al, 2014b).…”

Regulation of the human ether-a-gogo related gene (HERG) K+channels by reactive oxygen species

“…Reactive oxygen species (ROS) have been proposed as crucial regulators of cellular responses in both physiological and pathological states (1), such as cardiovascular (2) and neurodegenerative disorders (3), senescence (4), and programmed cell death (5). In the heart, ROS participate in the tissue damage observed under ischemia-reperfusion conditions (2).…”

“…In the heart, ROS participate in the tissue damage observed under ischemia-reperfusion conditions (2). Similarly, in the brain, where a large proportion of body oxygen is consumed, glutamateinduced neurotoxicity has been associated with the production of ROS, because free radical scavengers or inhibitors of ROSgenerating processes can prevent glutamate-induced neuronal degeneration (6,7).…”

Arrhythmogenic Effects of Arsenic Trioxide in Patients With Acute Promyelocytic Leukemia and an Electrophysiological Study in Isolated Guinea Pig Papillary Muscles

“…Additionally, ROS generated by As2O3, per se, could directly induce Ca 2+ overload. 23 In fact, we have already shown H2O2-induced triggered activities caused by DADs, contracture following a transient increase in developed tension, and an increase in [Ca 2+ ]i in fura-2-loaded guinea pig ventricular myocytes. 24 Beresewicz and Horackova have also shown that ROS can induce both EADs and DADs in rat and guinea pig ventricular myocytes.…”