CNS neurons express two distinct plasma membrane electron transport systems implicated in neuronal viability

Abstract

Trans-plasma membrane electron transport is critical for maintaining cellular redox balance and viability, yet few, if any, investigations have studied it in intact primary neurons. In this investigation, extracellular reduction of 2,6-dichloroindophenol (DCIP) and ferricyanide (FeCN) were measured as indicators of trans-plasma membrane electron transport by chick forebrain neurons. Neurons readily reduced DCIP, but not FeCN unless CoQ 1 , an exogenous ubiquinone analog, was added to the assays. CoQ 1 stimulated FeCN reduction in a dosedependent manner but had no effect on DCIP reduction. Reduction of both substrates was totally inhibited by e-maleimidocaproic acid (MCA), a membrane-impermeant thiol reagent, and slightly inhibited by superoxide dismutase. Diphenylene iodonium, a flavoenzyme inhibitor, completely inhibited FeCN reduction but had no affect on DCIP reduction, suggesting that these substrates are reduced by distinct redox pathways. The relationship between plasma membrane electron transport and neuronal viability was tested using the inhibitors MCA and capsaicin. MCA caused a dose-dependent decline in neuronal viability that closely paralleled its inhibition of both reductase activities. Similarly capsaicin, a NADH oxidase inhibitor, induced a rapid decline in neuronal viability. These results suggest that trans-plasma membrane electron transport helps maintain a stable redox environment required for neuronal viability.

Reactive oxygen species regulate quiescent T-cell apoptosis via the BH3-only proapoptotic protein BIM

“…Both PDTC and MnTMPyP modify NADPH/NADP oxidoreductase function, which is also a key component of the plasma membrane oxidoreductase system. 43,44 Thus, our study implicates cytoplasmic compartments in the generation of ROS that regulate BIM expression during NID in quiescent T cells. In addition, this study extends earlier studies in antigenstimulated T cells 33 to identify a role for ROS as key regulators of T-cell NID.…”

Nanomicellar formulation of coenzyme Q10 (Ubisol-Q10) effectively blocks ongoing neurodegeneration in the mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model: potential use as an adjuvant treatment in Parkinson's disease

“…Thus, CoQ 10 which is present in most cellular membranes as a fundamental component of oxidoreductase systems can also be a source of superoxide and, consequently, hydrogen peroxide. They are generated by auto-oxidation of ubisemiquinone, an intermediate radical of ubiquinone and/or quinol oxidoreduction cycle (Abramov et al, 2005;Hyun et al, 2006;Liu et al, 2005;Ushio-Fukai, 2006;Wright and Kuhn, 2002). Until recently, superoxide and hydrogen peroxide have been regarded, mainly, as harmful byproducts of mitochondrial respiration and targeted by various antioxidant-based strategies to control neurodegeneration.…”

“…Among the targets of hydrogen peroxide are the effectors of other signaling systems, namely, protein kinases and phosphatases (Thannickal and Fanburg, 2000;Wright and Kuhn, 2002). Zhu et al (2005) report that hydrogen peroxide alters membrane and cytoskeleton properties of astrocytes through the activation of p38 MAPK pathway.…”

Age-dependent neuroprotection of retinal ganglion cells by tempol-C8 acyl ester in a rat NMDA toxicity model

“…An example of this might be mitochondria-targeted TemPO conjugates with hemigramicidin as an "address molecule" [6]. However, free radicals can be generated not only in mitochondria but also in cell membranes, for example in the plasma respiratory chain called plasma membrane oxidoreductase (PmOR), which is also present in neuronal tissue [27]. We therefore conjectured that adding a lipophilic "address molecule" could increase both the amount and neuroprotective efficacy of tempol in membranes.…”