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Article ; Online: Historical origins of the discovery of mammalian nitric oxide (nitrogen monoxide) production/physiology/pathophysiology.

Lancaster, Jack R

2020 Volume 176, Page(s) 113793

Abstract: The award of the 1998 Nobel Prize in Physiology or Medicine to Robert F. Furchgott, Louis J. Ignarro, and Ferid Murad "for their discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system" highlighted the discovery of NO in ... ...

Abstract	The award of the 1998 Nobel Prize in Physiology or Medicine to Robert F. Furchgott, Louis J. Ignarro, and Ferid Murad "for their discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system" highlighted the discovery of NO in mammals. This breakthrough also coincided with the discoveries of the role of NO as a cytotoxic effector in the immune system and as an intercellular neurotransmitter in the nervous system. This brief overview describes the chronological development of this trilinear convergence in 1986-1988, including background chemistry and history of human/nitrogen oxide interactions in general.
MeSH term(s)	Animals ; Cardiovascular System/metabolism ; History, 20th Century ; History, 21st Century ; Humans ; Mammals/metabolism ; Nervous System/metabolism ; Nitric Oxide/history ; Nitric Oxide/metabolism ; Nitric Oxide/physiology ; Nobel Prize ; Signal Transduction
Chemical Substances	Nitric Oxide (31C4KY9ESH)
Language	English
Publishing date	2020-01-08
Publishing country	England
Document type	Historical Article ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2020.113793
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Article ; Online: How are nitrosothiols formed de novo in vivo?

Lancaster, Jack R

Archives of biochemistry and biophysics

2017 Volume 617, Page(s) 137–144

Abstract: The biological mechanisms of de novo formation of cellular nitrosothiols (as opposed to transnitrosation) are reviewed. The approach is to introduce chemical foundations for each mechanism, followed by evidence in biological systems. The general ... ...

Abstract	The biological mechanisms of de novo formation of cellular nitrosothiols (as opposed to transnitrosation) are reviewed. The approach is to introduce chemical foundations for each mechanism, followed by evidence in biological systems. The general categories include mechanisms involving nitrous acid, NO autoxidation and oxidant stress, redox active and inactive metal ions, and sulfide/persulfide. Important conclusions/speculations are that de novo cellular thiol nitrosation (1) is an oxidative process, and so should be considered within the family of other thiol oxidative modifications, (2) may not involve a single dominant process but depends on the specific conditions, (3) does not involve O
MeSH term(s)	Animals ; Cysteine/chemistry ; Heme/chemistry ; Humans ; Ions ; Iron/chemistry ; Ligands ; Metals/chemistry ; Nitric Oxide/chemistry ; Nitrogen/chemistry ; Nitrosation ; Oxidation-Reduction ; Oxidative Stress ; Oxygen/chemistry ; Protein Processing, Post-Translational ; S-Nitrosothiols/chemistry ; Signal Transduction
Chemical Substances	Ions ; Ligands ; Metals ; S-Nitrosothiols ; Nitric Oxide (31C4KY9ESH) ; Heme (42VZT0U6YR) ; Iron (E1UOL152H7) ; Cysteine (K848JZ4886) ; Nitrogen (N762921K75) ; Oxygen (S88TT14065)
Language	English
Publishing date	2017-03-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	523-x
ISSN	1096-0384 ; 0003-9861
ISSN (online)	1096-0384
ISSN	0003-9861
DOI	10.1016/j.abb.2016.10.015
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Article: Nitric oxide: a brief overview of chemical and physical properties relevant to therapeutic applications.

Lancaster, Jack R

Future science OA

2015 Volume 1, Issue 1, Page(s) FSO59

Abstract: Nitric oxide (nitrogen monoxide, •NO) has been intensively studied by chemists and physicists for over 200 years and thus there is an extensive database of information that determines its biological actions. This is a very brief overview of the chemical ... ...

Abstract	Nitric oxide (nitrogen monoxide, •NO) has been intensively studied by chemists and physicists for over 200 years and thus there is an extensive database of information that determines its biological actions. This is a very brief overview of the chemical and physical properties of •NO that are most relevant to Biology in general and to the development of •NO releasing materials in particular.
Language	English
Publishing date	2015-08-01
Publishing country	England
Document type	Review ; Journal Article
ISSN	2056-5623
ISSN	2056-5623
DOI	10.4155/fso.15.59
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Article ; Online: Direct measurement of nitric oxide (NO) production rates from enzymes using ozone-based gas-phase chemiluminescence (CL).

Sparacino-Watkins, Courtney E / Lancaster, Jack R

Nitric oxide : biology and chemistry

2021 Volume 117, Page(s) 60–71

Abstract: Nitric oxide (NO) chemiluminescence detectors (CLDs) are specialized and sensitive spectroscopic instruments capable of directly measuring NO flux rates. NO CLDs have been instrumental in the characterization of mammalian nitrite-dependent NO synthases. ... ...

Abstract	Nitric oxide (NO) chemiluminescence detectors (CLDs) are specialized and sensitive spectroscopic instruments capable of directly measuring NO flux rates. NO CLDs have been instrumental in the characterization of mammalian nitrite-dependent NO synthases. However, no detailed description of NO flux analysis using NO CLD is available. Herein, a detailed review of the NO CL methodology is provided with guidelines for measuring NO-production rates from aqueous samples, such as isolated enzymes or protein homogenates. Detailed description of the types of signals one can encounter, data processing, and potential pitfalls related to NO flux measurements will also be covered.
MeSH term(s)	Animals ; Equipment Design ; Kinetics ; Luminescent Measurements/methods ; Nitric Oxide/analysis ; Nitric Oxide/metabolism ; Nitric Oxide Synthase/analysis ; Nitric Oxide Synthase/metabolism ; Ozone/chemistry
Chemical Substances	Nitric Oxide (31C4KY9ESH) ; Ozone (66H7ZZK23N) ; Nitric Oxide Synthase (EC 1.14.13.39)
Language	English
Publishing date	2021-10-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1362794-6
ISSN	1089-8611 ; 1089-8603
ISSN (online)	1089-8611
ISSN	1089-8603
DOI	10.1016/j.niox.2021.10.001
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Article: How are nitrosothiols formed de novo inÂ vivo?

Lancaster, Jack R

Archives of biochemistry and biophysics. 2016,

2016

Abstract	The biological mechanisms of de novo formation of cellular nitrosothiols (as opposed to transnitrosation) are reviewed. The approach is to introduce chemical foundations for each mechanism, followed by evidence in biological systems. The general categories include mechanisms involving nitrous acid, NO autoxidation and oxidant stress, redox active and inactive metal ions, and sulfide/persulfide. Important conclusions/speculations are that de novo cellular thiol nitrosation (1) is an oxidative process, and so should be considered within the family of other thiol oxidative modifications, (2) may not involve a single dominant process but depends on the specific conditions, (3) does not involve O2 under at least some conditions, and (4) may serve to provide a âsubstrate poolâ of protein cysteine nitrosothiol which could, through subsequent enzymatic transnitrosation/denitrosation, be ârearrangedâ to accomplish the specificity and regulatory control required for effective post-translational signaling.
Keywords	autoxidation ; cysteine ; metal ions ; nitric oxide ; oxidants ; oxygen ; sulfides ; thiols
Language	English
Size	p. .
Publishing place	Elsevier Inc.
Document type	Article
Note	Pre-press version
ZDB-ID	523-x
ISSN	1096-0384 ; 0003-9861
ISSN (online)	1096-0384
ISSN	0003-9861
DOI	10.1016/j.abb.2016.10.015
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Mycobacterium tuberculosis DosS binds H2S through its Fe3+ heme iron to regulate the DosR dormancy regulon

Ritesh R. Sevalkar / Joel N. Glasgow / Martín Pettinati / Marcelo A. Marti / Vineel P. Reddy / Swati Basu / Elmira Alipour / Daniel B. Kim-Shapiro / Dario A. Estrin / Jack R. Lancaster, Jr. / Adrie J.C. Steyn

Redox Biology, Vol 52, Iss , Pp 102316- (2022)

2022

Abstract: ... we test the hypothesis that Mtb senses and responds to H2S via the DosS/T/R system. Using UV–Vis and EPR ...

Abstract	Mycobacterium tuberculosis (Mtb) senses and responds to host-derived gasotransmitters NO and CO via heme-containing sensor kinases DosS and DosT and the response regulator DosR. Hydrogen sulfide (H2S) is an important signaling molecule in mammals, but its role in Mtb physiology is unclear. We have previously shown that exogenous H2S can modulate expression of genes in the Dos dormancy regulon via an unknown mechanism(s). Here, we test the hypothesis that Mtb senses and responds to H2S via the DosS/T/R system. Using UV–Vis and EPR spectroscopy, we show that H2S binds directly to the ferric (Fe3+) heme of DosS (KDapp = 5.30 μM) but not the ferrous (Fe2+) form. No interaction with DosT(Fe2+-O2) was detected. We found that the binding of sulfide can slowly reduce the DosS heme iron to the ferrous form. Steered Molecular Dynamics simulations show that H2S, and not the charged HS− species, can enter the DosS heme pocket. We also show that H2S increases DosS autokinase activity and subsequent phosphorylation of DosR, and H2S-mediated increases in Dos regulon gene expression is lost in Mtb lacking DosS. Finally, we demonstrate that physiological levels of H2S in macrophages can induce DosR regulon genes via DosS. Overall, these data reveal a novel mechanism whereby Mtb senses and responds to a third host gasotransmitter, H2S, via DosS(Fe3+). These findings highlight the remarkable plasticity of DosS and establish a new paradigm for how bacteria can sense multiple gasotransmitters through a single heme sensor kinase.
Keywords	Hydrogen sulfide ; Tuberculosis ; Dormancy regulon ; Two-component system ; DosS ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Endogenous generation of nitro-fatty acid hybrids having dual nitrate ester (RONO2) and nitroalkene (RNO2) substituents

Marco Fazzari / Steven R. Woodcock / Pascal Rowart / Karina Ricart / Jack R. Lancaster, Jr. / Rakesh Patel / Dario A. Vitturi / Bruce A. Freeman / Francisco J. Schopfer

Redox Biology, Vol 41, Iss , Pp 101913- (2021)

2021

Abstract: Organic nitrate esters, long-recognized therapies for cardiovascular disorders, have not been detected biologically. We characterize in rat stomach unsaturated fatty acid nitration reactions that proceed by generation of nitro-nitrate intermediates (NO2– ... ...

Abstract	Organic nitrate esters, long-recognized therapies for cardiovascular disorders, have not been detected biologically. We characterize in rat stomach unsaturated fatty acid nitration reactions that proceed by generation of nitro-nitrate intermediates (NO2–ONO2-FA) via oxygen and nitrite dependent reactions. NO2–ONO2-lipids represent ∼70% of all nitrated lipids in the stomach and they decay in vitro at neutral or basic pH by the loss of the nitrate ester group (-ONO2) from the carbon backbone upon deprotonation of the α-carbon (pKa ∼7), yielding nitrate, nitrite, nitrosative species, and an electrophilic fatty acid nitroalkene product (NO2-FA). Of note, NO2-FA are anti-inflammatory and tissue-protective signaling mediators, which are undergoing Phase II trials for the treatment of kidney and pulmonary diseases. The decay of NO2–ONO2-FA occurs during intestinal transit and absorption, leading to the formation of NO2-FA that were subsequently detected in circulating plasma triglycerides. These observations provide new insight into unsaturated fatty acid nitration mechanisms, identify nitro-nitrate ester-containing lipids as intermediates in the formation of both secondary nitrogen oxides and electrophilic fatty acid nitroalkenes, and expand the scope of endogenous products stemming from metabolic reactions of nitrogen oxides.
Keywords	Nitro-nitrate-fatty acid ; Nitro-conjugated linoleic acid ; Conjugated linoleic acid ; Fatty acid nitroalkene ; Nitrate ester ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Subject code	540 ; 571
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The use of diaminofluorescein for nitric oxide detection: Conceptual and methodological distinction between NO and nitrosation.

Lancaster, Jack R

Free radical biology & medicine

2010 Volume 49, Issue 6, Page(s) 1145

MeSH term(s)	Fluorescein/chemistry ; Fluorescent Dyes/chemistry ; Nitric Oxide/analysis ; Nitric Oxide/chemistry ; Nitrogen Oxides/chemistry ; Nitrosation ; Terminology as Topic
Chemical Substances	4,5-diaminofluorescein ; Fluorescent Dyes ; Nitrogen Oxides ; nitrogen trioxide (16E0524PXI) ; Nitric Oxide (31C4KY9ESH) ; Fluorescein (TPY09G7XIR)
Language	English
Publishing date	2010-09-15
Publishing country	United States
Document type	Letter
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2010.06.015
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Article ; Online: Mitochondria-meditated pathways of organ failure upon inflammation

Andrey V. Kozlov / Jack R. Lancaster, Jr. / Andras T. Meszaros / Adelheid Weidinger

Redox Biology, Vol 13, Iss C, Pp 170-

2017 Volume 181

Abstract: Liver failure induced by systemic inflammatory response (SIRS) is often associated with mitochondrial dysfunction but the mechanism linking SIRS and mitochondria-mediated liver failure is still a matter of discussion. Current hypotheses suggest that ... ...

Abstract	Liver failure induced by systemic inflammatory response (SIRS) is often associated with mitochondrial dysfunction but the mechanism linking SIRS and mitochondria-mediated liver failure is still a matter of discussion. Current hypotheses suggest that causative events could be a drop in ATP synthesis, opening of mitochondrial permeability transition pore, specific changes in mitochondrial morphology, impaired Ca2+ uptake, generation of mitochondrial reactive oxygen species (mtROS), turnover of mitochondria and imbalance in electron supply to the respiratory chain. The aim of this review is to critically analyze existing hypotheses, in order to highlight the most promising research lines helping to prevent liver failure induced by SIRS. Evaluation of the literature shows that there is no consistent support that impaired Ca++ metabolism, electron transport chain function and ultrastructure of mitochondria substantially contribute to liver failure. Moreover, our analysis suggests that the drop in ATP levels has protective rather than a deleterious character. Recent data suggest that the most critical mitochondrial event occurring upon SIRS is the release of mtROS in cytoplasm, which can activate two specific intracellular signaling cascades. The first is the mtROS-mediated activation of NADPH-oxidase in liver macrophages and endothelial cells; the second is the acceleration of the expression of inflammatory genes in hepatocytes. The signaling action of mtROS is strictly controlled in mitochondria at three points, (i) at the site of ROS generation at complex I, (ii) the site of mtROS release in cytoplasm via permeability transition pore, and (iii) interaction with specific kinases in cytoplasm. The systems controlling mtROS-signaling include pro- and anti-inflammatory mediators, nitric oxide, Ca2+ and NADPH-oxidase. Analysis of the literature suggests that further research should be focused on the impact of mtROS on organ failure induced by inflammation and simultaneously providing a new theoretical basis for a targeted therapy of overwhelmed inflammatory response.
Keywords	Liver failure ; Mitochondria ; Reactive oxygen species ; Signaling ; Inflammation ; Medicine (General) ; R5-920 ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2017-10-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Quantitation of spin probe-detectable oxidants in cells using electron paramagnetic resonance spectroscopy: To probe or to trap?

Gotham, John P / Li, Rui / Tipple, Trent E / Lancaster, Jack R / Liu, Taiming / Li, Qian

Free radical biology & medicine

2020 Volume 154, Page(s) 84–94

Abstract: Electron Paramagnetic Resonance (EPR) spectroscopy coupled with spin traps/probes enables quantitative determination of reactive nitrogen and oxygen species (RNOS). Even with numerous studies using spin probes, the methodology has not been rigorously ... ...

Abstract	Electron Paramagnetic Resonance (EPR) spectroscopy coupled with spin traps/probes enables quantitative determination of reactive nitrogen and oxygen species (RNOS). Even with numerous studies using spin probes, the methodology has not been rigorously investigated. The autoxidation of spin probes has been commonly overlooked. Using the spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH), the present study has tested the effects of metal chelators, temperature, and oxygen content on the autoxidation of spin probes, where an optimized condition is refined for cell studies. The apparent rate of CMH autoxidation under this condition is 7.01 ± 1.60 nM/min, indicating low sensitivity and great variation of the CMH method and that CMH autoxidation rate should be subtracted from the generation rate of CMH-detectable oxidants (simplified as oxidants below) in samples. Oxidants in RAW264.7 cells are detected at an initial rate of 4.0 ± 0.7 pmol/min/10
MeSH term(s)	Cold Temperature ; Cyclic N-Oxides ; Electron Spin Resonance Spectroscopy ; Free Radicals ; Oxidants ; Oxygen ; Reactive Oxygen Species ; Spin Labels
Chemical Substances	Cyclic N-Oxides ; Free Radicals ; Oxidants ; Reactive Oxygen Species ; Spin Labels ; Oxygen (S88TT14065)
Language	English
Publishing date	2020-05-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	807032-5
ISSN	1873-4596 ; 0891-5849
ISSN (online)	1873-4596
ISSN	0891-5849
DOI	10.1016/j.freeradbiomed.2020.04.020
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