Role of TRP Channels in Oxidative Stress

Gröschner, Klaus; Rosker, Christian; Lukas, Michael

doi:10.1002/0470862580.ch16

Cited by 67 publications

(44 citation statements)

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“…tBHP increases cation currents in porcine aortic endothelial cells, an effect that has also been observed in cells overexpressing TRPC3 or TRPC4 channels [148]. The subsequent finding that the activating effect of oxidants in TRPC3 expressing cells can be inhibited by the U73122, an inhibitor of phospholipase C (PLC) [149], might suggest that activation does not involve direct oxidation of thiols in TRPC proteins, although a required costimulatory role of phospholipids such as diacylglycerol (DAG) together with a direct oxidant effect cannot be ruled out. Because ROS are known to inhibit protein phosphatases such as PP2A, the effects of increased ion channel phosphorylation versus a direct oxidation of ion channel thiol-groups need to be taken into account.…”

Section: Redox Regulation Of Trpc Channelsmentioning

confidence: 85%

Redox regulation of calcium ion channels: Chemical and physiological aspects

et al. 2011

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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).

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Section: Redox Regulation Of Trpc Channelsmentioning

confidence: 85%

Redox regulation of calcium ion channels: Chemical and physiological aspects

et al. 2011

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“…For instance, it is well established that TRPC3 participates in oxidative stress signaling, a recognized factor in vascular inflammation (19,20). In bovine aortic endothelial cells migration is inhibited by lysophosphatidylcholine, a major component of oxidized low density lipoprotein, through a mechanism that requires sustained calcium influx mediated by the sequential activation of TRPC6 and TRPC5 (21).…”

Section: Discussionmentioning

confidence: 99%

Increased size and cellularity of advanced atherosclerotic lesions in mice with endothelial overexpression of the human TRPC3 channel

Smedlund

Birnbaumer

Vázquez

2015

Proc. Natl. Acad. Sci. U.S.A.

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In previous in vitro studies, we showed that Transient Receptor Potential Canonical 3 (TRPC3), a calcium-permeable, nonselective cation channel endowed with high constitutive function, is an obligatory component of the inflammatory signaling that controls expression of the vascular cell adhesion molecule-1 (VCAM-1) and monocyte adhesion to coronary artery endothelial cells. Also, TRPC3 expression in these cells was found to be up-regulated by proatherogenic factors, which enhanced inflammation and VCAM-1 expression. However, it remained to be determined whether these in vitro findings were of relevance to atherosclerotic lesion development in vivo. To answer this important question in the present work, we generated mice with endothelial-specific overexpression of human TRPC3 in an Apoe knockout background (TgEST3ApoeKO) and examined lesions in the aortic sinus following 10 and 16 wk on a high-fat diet. No significant differences were found in size or complexity of early stage lesions (10 wk). However, advanced plaques (16 wk) from TgEST3ApoeKO mice exhibited a significant increase in size and macrophage content compared with nontransgenic littermate controls. Remarkably, this change was correlated with increased VCAM-1 and phospho-IkBα immunoreactivity along the endothelial lining of lesions from transgenic animals compared with controls. These findings validate the in vivo relevance of previous in vitro findings and represent, to our knowledge, the first in vivo evidence for a proatherogenic role of endothelial TRPC3.TRPC3 channels | atherosclerosis | endothelial inflammation

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“…This phospholipid stabilizes the activity of ROMK (15,20), and oxidative stress has been shown to activate its breakdown through activation of PLC (26,38). Tubules were preincubated for 10 min or more with PLC inhibitor U73122 (33) at a concentration of 5 M. This compound was previously shown to prevent the stimulation of TRPC3 channels by t-BHP, an effect thought to involve activation of PLC␥ and depletion of plasma-membrane PIP2 (14). more stable than the principal cell under whole-cell voltage clamp and enables the continuous measurement of ROMK-mediated currents since the background conductance is very low.…”

Section: Resultsmentioning

confidence: 99%