Functionality of nitrated acetylcholine receptor: The two‐step formation of nitrotyrosines reveals their differential role in effectors binding

Négrerie, Michel; Martin, Jean−Louis; Nghiêm, Hoàng‐Oanh

doi:10.1016/j.febslet.2005.03.084

Cited by 3 publications

(1 citation statement)

References 25 publications

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“…One possibility is that continued exposure to elevated levels of superoxide directly damages G protein/receptor-mediated signal transduction mechanisms in aortas from rats on a HS diet, independent of effects on NO availability. However, it is conceivable that destruction of NO by elevated levels of superoxide could also affect [Ca 2ϩ ] i signaling mechanisms, e.g., by nitration of the receptor via the actions of peroxynitrite formed by combination of NO with superoxide radicals (20).…”

Section: Camentioning

confidence: 99%

Role of superoxide and angiotensin II suppression in salt-induced changes in endothelial Ca²⁺ signaling and NO production in rat aorta

Zhu¹,

Drenjančević-Perić²,

McEwen³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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Male Sprague-Dawley rats were maintained on a low-salt (LS) diet (0.4% NaCl) or changed to a high-salt (HS) diet (4% NaCl) for 3 days. Increases in intracellular Ca 2ϩ ([Ca 2ϩ ]i) in response to methacholine (10 M) and histamine (10 M) were significantly attenuated in aortic endothelial cells from rats fed a HS diet, whereas thapsigargin (10 M)-induced increases in [Ca 2ϩ ]i were unaffected. Methacholineinduced nitric oxide (NO) production was eliminated in endothelial cells of aortas from rats fed a HS diet. Low-dose ANG II infusion (5 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 iv) for 3 days prevented impaired [Ca 2ϩ ]i signaling response to methacholine and histamine and restored methacholineinduced NO production in aortas from rats on a HS diet. Adding Tempol (500 M) to the tissue bath to scavenge superoxide anions increased NO release and caused N -nitro-L-arginine methyl estersensitive vascular relaxation in aortas from rats fed a HS diet but had no effect on methacholine-induced Ca 2ϩ responses. Chronic treatment with Tempol (1 mM) in the drinking water restored NO release, augmented vessel relaxation, and increased methacholine-induced Ca 2ϩ responses significantly in aortas from rats on a HS diet but not in aortas from rats on a LS diet. These findings suggest that 1) agonist-induced Ca 2ϩ responses and NO levels are reduced in aortas of rats on a HS diet; 2) increased vascular superoxide levels contribute to NO destruction, and, eventually, to impaired Ca 2ϩ signaling in the vascular endothelial cells; and 3) reduced circulating ANG II levels during elevated dietary salt lead to elevated superoxide levels, impaired endothelial Ca 2ϩ signaling, and reduced NO production in the endothelium. endothelium; sodium; dietary salt intake; vascular relaxation; nitric oxide A VARIETY OF AGENTS, including muscarinic agonists such as ACh, dilate blood vessels by stimulating the synthesis of nitric oxide (NO) by endothelial NO synthase. Endothelial cell activation in response to agonists and autacoids leads to NO formation via receptor-mediated increases in intracellular calcium ion concentration ([Ca 2ϩ ] i ). However, emerging evidence indicates that endothelial NO synthase activity can be affected by a variety of other mechanisms that are independent of [Ca 2ϩ ] i (7,12,21,26,27). This raises the possibility that changes in NO production under some physiological conditions may be independent of changes in endothelial [Ca 2ϩ ] i . Endothelium-dependent relaxation in response to ACh is impaired in the aorta, resistance arteries, and microvessels of rats fed a high-salt (HS) diet (2-5, 15, 16, 18, 28). Elevated dietary salt intake causes suppression of plasma ANG II levels (8, 9), and previous studies (18,30,31) have demonstrated that the impaired vascular relaxation in Sprague-Dawley rats fed a HS diet can be prevented by a continuous intravenous infusion of a low dose of ANG II to maintain normal circulating levels of ANG II.In the present study, we tested the hypothesis that receptormediated increases in [Ca 2ϩ ] i and/or...

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Section: Camentioning

confidence: 99%

Role of superoxide and angiotensin II suppression in salt-induced changes in endothelial Ca²⁺ signaling and NO production in rat aorta

Zhu¹,

Drenjančević-Perić²,

McEwen³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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Identifying Residues in Antigenic Determinants by Chemical Modification

Reisner

Lundblad

2009

Epitope Mapping Protocols

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Chemical modification of the side chains of amino acid residues was one of the first methods developed to investigate epitopes in protein antigens. The principle of the method is that alteration of the structure of a key residue of an epitope by a chemical modification will alter reactivity with antibody by affecting either specificity or avidity or both. Chemical modification has the advantage that it can be applied to discontinuous as well as continuous epitopes and may be of value in identifying cryptic epitopes. We consider here the several recent studies that have applied site-specific chemical modification to the identification of epitopes on antigens, including the use of formaldehyde, glutaraldehyde, and acid anhydrides, to produce allergoids where determinants important to reaction with IgE are modified but the ability to elicit an IgG response is retained. It is noteworthy that modification of amino groups with charge reversal appears to be the most useful approach. The approach to the use of site-specific chemical modification as a tool for the study of protein function is discussed, and emphasis is placed on the necessity to (1) validate the specificity of modification and (2) assess potential conformational change that may occur secondary to modification. Finally, a list of chemical reagents used for protein modification is presented, together with properties and references to use.

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Structural answers and persistent questions about how nicotinic receptors work

Wells¹

2008

Front Biosci

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The electron diffraction structure of nicotinic acetylcholine receptor (nAChR) from Torpedo marmorata and the X-ray crystallographic structure of acetylcholine binding protein (AChBP) are providing new answers to persistent questions about how nAChRs function as biophysical machines and as participants in cellular and systems physiology. New high-resolution information about nAChR structures might come from advances in crystallography and NMR, from extracellular domain nAChRs as high fidelity models, and from prokaryotic nicotinoid proteins. At the level of biophysics, structures of different nAChRs with different pharmacological profiles and kinetics will help describe how agonists and antagonists bind to orthosteric binding sites, how allosteric modulators affect function by binding outside these sites, how nAChRs control ion flow, and how large cytoplasmic domains affect function. At the level of cellular and systems physiology, structures of nAChRs will help characterize interactions with other cellular components, including lipids and trafficking and signaling proteins, and contribute to understanding the roles of nAChRs in addiction, neurodegeneration, and mental illness. Understanding nAChRs at an atomic level will be important for designing interventions for these pathologies. KeywordsAcetylcholine; Addiction; Neurodegeneration; Nicotine; Protein Design; Protein Folding; Protein Structure; Cys-Loop Receptors; Review INTRODUCTIONNicotinic acetylcholine receptors (nAChRs) are integral-membrane, neurotransmitteractivated ion channels in the central and peripheral nervous systems that participate in signal transmission associated with the physiological release of acetylcholine (1). As cationselective ion channels, they depolarize transmembrane voltage when they transition from the closed resting state to the open cation-conducting state by binding agonist. Continued exposure to agonist causes transition from the open state to the closed desensitized state. More than four decades of research have answered many structural questions about nAChRs. Reviews published across these decades reveal the progression of questions and answers (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Current understanding of the structural basis of how nAChRs work is relatively advanced compared to other areas of ion channel biophysics (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Despite this level of understanding, however, questions persist, not only about biophysical properties but also about the structural basis of how nAChRs affect cellular and systems physiology (28). NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptBy reviewing research literature published primarily between 2003 and mid-2007, the goals of this review are to describe the current state of understanding of the structures of nAChRs and to describe questions for which atomic-level structural answers still await. WHICH STRUCTURAL FEATURES DEFINE NACHRS AND OTHER CYS-LOOP RECEPTORS?Mammalian genomes contain 16 nAChR subunits ...

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Functionality of nitrated acetylcholine receptor: The two‐step formation of nitrotyrosines reveals their differential role in effectors binding

Cited by 3 publications

References 25 publications

Role of superoxide and angiotensin II suppression in salt-induced changes in endothelial Ca²⁺ signaling and NO production in rat aorta

Role of superoxide and angiotensin II suppression in salt-induced changes in endothelial Ca²⁺ signaling and NO production in rat aorta

Identifying Residues in Antigenic Determinants by Chemical Modification

Structural answers and persistent questions about how nicotinic receptors work

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Functionality of nitrated acetylcholine receptor: The two‐step formation of nitrotyrosines reveals their differential role in effectors binding

Cited by 3 publications

References 25 publications

Role of superoxide and angiotensin II suppression in salt-induced changes in endothelial Ca2+ signaling and NO production in rat aorta

Role of superoxide and angiotensin II suppression in salt-induced changes in endothelial Ca2+ signaling and NO production in rat aorta

Identifying Residues in Antigenic Determinants by Chemical Modification

Structural answers and persistent questions about how nicotinic receptors work

Contact Info

Product

Resources

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Role of superoxide and angiotensin II suppression in salt-induced changes in endothelial Ca²⁺ signaling and NO production in rat aorta

Role of superoxide and angiotensin II suppression in salt-induced changes in endothelial Ca²⁺ signaling and NO production in rat aorta