scholarly journals Activation of nicotinic acetylcholine receptor prevents the production of reactive oxygen species in fibrillar β amyloid peptide (1-42)-stimulated microglia

2008 ◽  
Vol 40 (1) ◽  
pp. 11 ◽  
Author(s):  
Ju Hyun Moon ◽  
Soo Yoon Kim ◽  
Hwan Goo Lee ◽  
Seung U. Kim ◽  
Yong Beom Lee
Keyword(s):  
Reactive Oxygen Species ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Reactive Oxygen ◽  
Amyloid Peptide ◽  
Oxygen Species ◽  
Nicotinic Acetylcholine ◽  
Β Amyloid ◽  
Β Amyloid Peptide

scholarly journals Microglia enhance β-amyloid peptide-induced toxicity in cortical and mesencephalic neurons by producing reactive oxygen species

2002 ◽  
Vol 83 (4) ◽  
pp. 973-983 ◽  
Author(s):  
Liya Qin ◽  
Yuxin Liu ◽  
Cynthia Cooper ◽  
Bin Liu ◽  
Belinda Wilson ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Amyloid Peptide ◽  
Oxygen Species ◽  
Β Amyloid ◽  
Β Amyloid Peptide

Amentoflavone: A Bifunctional Metal Chelator that Controls the Formation of Neurotoxic Soluble Aβ42 Oligomers

2020 ◽  
Author(s):  
Liang Sun ◽  
Anuj K. Sharma ◽  
Byung-Hee Han ◽  
Liviu M. Mirica
Keyword(s):  
Reactive Oxygen Species ◽  
Metal Ions ◽  
Antioxidant Properties ◽  
Reactive Oxygen ◽  
Amyloid Plaques ◽  
Transition Metal Ions ◽  
Oxygen Species ◽  
High Affinity ◽  
Amyloid Aβ ◽  
Β Amyloid

<p>Alzheimer's disease (AD) is the most common neurodegenerative disorder, yet the cause and progression of this disorder are not completely understood. While the main hallmark of AD is the deposition of amyloid plaques consisting of the β-amyloid (Aβ) peptide, transition metal ions are also known to play a significant role in disease pathology by expediting the formation of neurotoxic soluble β-amyloid (Aβ) oligomers, reactive oxygen species (ROS), and oxidative stress. Thus, bifunctional metal chelators that can control these deleterious properties are highly desirable. Herein, we show that amentoflavone (AMF) – a natural biflavonoid compound, exhibits good metal-chelating properties, especially for chelating Cu<sup>2+</sup> with very high affinity (pCu<sub>7.4</sub> = 10.44). In addition, AMF binds to Aβ fibrils with a high affinity (<i>K<sub>i</sub></i> = 287 ± 20 nM) – as revealed by a competition thioflavin T (ThT) assay, and specifically labels the amyloid plaques <i>ex vivo</i> in the brain sections of transgenic AD mice – as confirmed via immunostaining with an Ab antibody. The effect of AMF on Aβ<sub>42</sub> aggregation and disaggregation of Aβ<sub>42</sub> fibrils was also investigated, to reveal that AMF can control the formation of neurotoxic soluble Aβ<sub>42</sub> oligomers, both in absence and presence of metal ions, and as confirmed via cell toxicity studies. Furthermore, an ascorbate consumption assay shows that AMF exhibits potent antioxidant properties and can chelate Cu<sup>2+</sup> and significantly diminish the Cu<sup>2+</sup>-ascorbate redox cycling and reactive oxygen species (ROS) formation. Overall, these studies strongly suggest that AMF acts as a bifunctional chelator that can interact with various Aβ aggregates and reduce their neurotoxicity, can also bind Cu<sup>2+</sup> and mediate its deleterious redox properties, and thus AMF has the potential to be a lead compound for further therapeutic agent development for AD. </p>

Effect of reactive oxygen species on NH 4 + permeation in Xenopus laevis oocytes

2002 ◽  
Vol 282 (6) ◽  
pp. C1445-C1453 ◽  
Author(s):  
Marc Cougnon ◽  
Samia Benammou ◽  
Franck Brouillard ◽  
Philippe Hulin ◽  
Gabrielle Planelles
Keyword(s):  
Reactive Oxygen Species ◽  
Xenopus Laevis ◽  
Reactive Oxygen ◽  
Membrane Conductance ◽  
Xenopus Laevis Oocytes ◽  
Oxygen Species ◽  
Cation Conductance ◽  
Β Amyloid ◽  
Oocyte Membrane ◽  
Ros Scavengers

To investigate the effects of reactive oxygen species (ROS) on NH[Formula: see text]permeation in Xenopus laevis oocytes, we used intracellular double-barreled microelectrodes to monitor the changes in membrane potential ( V m) and intracellular pH (pHi) induced by a 20 mM NH4Cl-containing solution. Under control conditions, NH4Cl exposure induced a large membrane depolarization (to V m = 4.0 ± 1.5 mV; n = 21) and intracellular acidification [reaching a change in pHi(ΔpHi) of 0.59 ± 0.06 pH units in 12 min]; the initial rate of cell acidification (dpHi/d t) was 0.06 ± 0.01 pH units/min. Incubation of the oocytes in the presence of H2O2 or β-amyloid protein had no marked effect on the NH4Cl-induced ΔpHi. By contrast, in the presence of photoactivated rose bengal (RB), tert-butyl-hydroxyperoxide ( t-BHP), or xanthine/xanthine oxidase (X/XO), the same experimental maneuver induced significantly greater ΔpHi and dpHi/d t. These increases in ΔpHiand dpHi/d t were prevented by the ROS scavengers histidine and desferrioxamine, suggesting involvement of the reactive species 1ΔgO2 and ·OH. Using the voltage-clamp technique to identify the mechanism underlying the ROS-measured effects, we found that RB induced a large increase in the oocyte membrane conductance ( G m). This RB-induced G m increase was prevented by 1 mM diphenylamine-2-carboxylate (DPC) and by a low Na+concentration in the bath. We conclude that RB, t-BHP, and X/XO enhance NH[Formula: see text] influx into the oocyte via activation of a DPC-sensitive nonselective cation conductance pathway.

scholarly journals Implication of the small GTPase Rac1 in the generation of reactive oxygen species in response to β-amyloid in C6 astroglioma cells

2002 ◽  
Vol 366 (3) ◽  
pp. 937-943 ◽  
Author(s):  
Mina LEE ◽  
Hye-Jin YOU ◽  
Sung-Hoon CHO ◽  
Chang-Hoon WOO ◽  
Min-Hyuk YOO ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Leukotriene B4 ◽  
Small Gtpase ◽  
Cell Surface Receptor ◽  
Oxygen Species ◽  
Exogenous Application ◽  
Essential Components ◽  
Β Amyloid ◽  
Astroglioma Cells

Exogenous application of β-amyloid (Aβ25—35, a fragment of Aβ1—42) significantly elevated levels of reactive oxygen species (ROS) in C6 astroglioma cells, as measured by confocal microscopic analysis of H2O2-sensitive 2′,7′-dichlorofluorescin fluorescence. Subsequent characterization of the signalling pathway revealed that expression of RacN17, a dominant-negative Rac1 mutant, completely blocked Aβ25—35-induced generation of ROS, which is indicative of the crucial role played by Rac GTPase in this process. To better understand the downstream mediators affected by Rac, we assessed the degree to which inhibition of cytosolic phospholipase A2 (cPLA2) and 5-lipoxygenase (5-LO) contributed to the response and found that inhibition of either enzyme completely blocked Aβ25—35-induced ROS generation, indicating its dependence on arachidonic acid synthesis and metabolism to leukotrienes (e.g. leukotriene B4). Consistent with those findings, Aβ25—35 Rac-dependently stimulated translocation of 5-LO to the nuclear envelope and increased intracellular levels of leukotriene B4, while exogenous application of leukotriene B4 increased intracellular H2O2 via BLT, its cell-surface receptor. In addition to the aforementioned downstream mediators, inhibition of phosphoinositide 3-kinase (PI 3-kinase), an enzyme situated upstream of Rac, also completely blocked Aβ25—35-induced H2O2 generation. Our findings thus demonstrate that PI 3-kinase, Rac, cPLA2 and 5-LO are all essential components of the β-amyloid signaling cascade leading to generation of ROS.

scholarly journals Cortical α7 Nicotinic Acetylcholine Receptor and β-Amyloid Levels in Early Alzheimer Disease

2009 ◽  
Vol 66 (5) ◽  
Author(s):  
Milos D. Ikonomovic ◽  
Lynn Wecker ◽  
Eric E. Abrahamson ◽  
Joanne Wuu ◽  
Scott E. Counts ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine ◽  
Β Amyloid

β-Amyloid Peptide Activates Non-α7 Nicotinic Acetylcholine Receptors in Rat Basal Forebrain Neurons

2003 ◽  
Vol 90 (5) ◽  
pp. 3130-3136 ◽  
Author(s):  
Wen Fu ◽  
Jack H. Jhamandas
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Basal Forebrain ◽  
Single Channel ◽  
Amyloid Peptide ◽  
Nicotinic Acetylcholine ◽  
Whole Cell ◽  
Β Amyloid ◽  
Forebrain Neurons ◽  
Β Amyloid Peptide ◽  
Α7 Nachrs

Alzheimer's disease (AD) is a progressive neurodegenerative condition characterized by profound deficits in memory and cognitive function. Neuropathological hallmarks of the disease include a loss of basal forebrain cholinergic neurons and the deposition of β-amyloid peptide (Aβ) in neuritic plaques. At a cellular level, considerable attention has focused on a study of Aβ interactions with the neuronal nicotinic acetylcholine receptor (nAChR) subtypes. In this study, using cell-attached and outside-out single channel recordings from acutely dissociated rat basal forebrain neurons, we report that Aβ and nicotine activate nAChRs with two distinct levels of single-channel conductance. Whole cell recordings from these neurons reveal Aβ and nicotine, in a concentration-dependent and reversible manner, evoke brisk depolarizing responses and an inward current. The effects of Aβ on both single channel and whole cell are blocked by the noncompetitive nAChR antagonist mecamylamine and competitive nAChR antagonist dihydro-beta-erythroidine, but not the specific α7-selective nAChR antagonist methyllycaconitine, indicating that Aβ activated non-α7 nAChRs on basal forebrain neurons. In addition, the non-α7 nAChR agonists UB-165, epibatidine, and cytisine, but not the selective α7 agonist AR-R17779, induced similar responses as Aβ and nicotine. Thus non-α7 nAChRs may also represent a novel target in mediating the effects of Aβ in AD.

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