Redox regulation of calcium ion channels: Chemical and physiological aspects

Abstract

a b s t r a c tReactive oxygen species (ROS) are increasingly recognized as second messengers in many cellular processes. While high concentrations of oxidants damage proteins, lipids and DNA, ultimately resulting in cell death, selective and reversible oxidation of key residues in proteins is a physiological mechanism that can transiently alter their activity and function. Defects in ROS producing enzymes cause disturbed immune response and disease.Changes in the intracellular free Ca 2+ concentration are key triggers for diverse cellular functions. Ca 2+ homeostasis thus needs to be precisely tuned by channels, pumps, transporters and cellular buffering systems. Alterations of these key regulatory proteins by reversible or irreversible oxidation alter the physiological outcome following cell stimulation. It is therefore necessary to understand which proteins are regulated and if this regulation is relevant in a physiological-and/or pathophysiological context. Because ROS are inherently difficult to identify and to measure, we first review basic oxygen redox chemistry and methods of ROS detection with special emphasis on electron paramagnetic resonance (EPR) spectroscopy. We then focus on the present knowledge of redox regulation of Ca 2+ permeable ion channels such as voltage-gated (CaV) Ca 2+ channels, transient receptor potential (TRP) channels and Orai channels.© 2011 Elsevier Ltd. All rights reserved. Basic redox chemistry of oxygenMany chemical processes are linked to the exchange of electrons between two or more molecular entities. The transfer of one (or more) electron(s) is associated with oxidation (loss of electron) and reduction (gain of electron) of the components. Such reactions are also known as redox reactions. The processes of reactive oxygen species (ROS) formation and elimination are exclusively of redox nature.Molecular oxygen is the precursor of all ROS. It contains two unpaired electrons in separate (antibonding) orbitals in its outer electron sphere and is thus, by definition, a radical. Radicals have at least one unpaired electron in their orbital system and usually show high reactivity; transition metal ions also may have unpaired electrons, but are not called radicals. Although having radical character, molecular oxygen is chemically rather inert (luckily!), because high * Corresponding authors at: Institut für Biophysik, Gebäude 58, Universität des Saarlandes, D-66421 Homburg/Saar, Germany. Tel.: +49 6841 1626453; fax: +49 6841 1626060.E-mail addresses: ivan.bogeski@uks.eu (I. Bogeski), barbara.niemeyer@uks.eu (B.A. Niemeyer).

Blockade of NOX2 and STIM1 signaling limits lipopolysaccharide-induced vascular inflammation

“…Oxidative signaling and Ca 2+ homeostasis are tightly linked cellular processes mediating control over signal transduction, metabolism, transcriptional regulation, cell proliferation, and cell death (12,13). Oxidants are implicated in modulating intracellular Ca 2+ release channels and Ca 2+ entry channels in the plasma membrane (14)(15)(16).…”

Redox regulation of the yeast voltage-gated Ca2+ channel homolog Cch1p by glutathionylation of specific cysteine residues

“…The redox state of the cell also controls ion channels/transporters, and these transporters can also reciprocally regulate the redox environment (Bogeski et al, 2010(Bogeski et al, , 2011Puigpinós et al, 2015). Thus, in higher organisms, different members of Ca 2+ -conducting ion channels/transporters are known to be redox sensitive (Kozai et al, 2014;Todorovic and Jevtovic-Todorovic, 2014).…”

Oxidative Stress in Human Health and Disease

“…The increased Ca 2 + flux can also promote NADPH oxidase activity to produce more ROS (154). As previously noted, low levels of ROS generated by glucose metabolism, is important for glucose stimulated insulin secretion while higher levels damage cells of the Islets and induce insulin resistance through activation of redox sensitive intracellular signaling pathways (6). Changes in glucose and lipid metabolism contribute to ROS generation through the formation of diacylglycerol (DAG), advanced glycation end products (AGE), increased polyol formation and increased hexosamine pathway flux (155,156).…”

“…These signals begin outside of the cell, with ligand receptor interaction, followed by conformational changes in the receptor that enables it to be activated through phosphorylation by kinases and inhibition of phosphatases (3,4). The signal is then carried by second messengers for transduction into the cell nucleus (5,6). Transcription factors constitute the terminal signal receivers to initiate gene expression critical for normal cell function.…”