Abstract:
:Nitric oxide (NO(•); nitrogen monoxide) is known to be a critical regulator of cell and tissue function through mechanisms that utilize its unique physicochemical properties as a small and uncharged free radical with limited reactivity. Here, the basic chemistry and biochemistry of NO(•) are summarized through the description of its chemical reactivity, biological sources, physiological and pathophysiological levels, and cellular transport. The complexity of the interactions of NO(•) with biotargets, which vary from irreversible second-order reactions to reversible formation of nonreactive and reactive nitrosyl complexes, is noted. Emphasis is placed on the kinetics and physiological consequences of the reactions of NO(•) with its better characterized biotargets. These targets are soluble guanylate cyclase (sCG), oxyhemoglobin/hemoglobin (HbO(2)/Hb) and cytochrome c oxidase (CcOx), all of which are ferrous heme proteins that react with NO(•) with second-order rate constants approaching the diffusion limit (k(on) approximately 10(7) to 10(8) M(-1) s(-1)). Likewise, the biotarget responsible for the most described pathophysiological actions of NO(•) is the superoxide anion radical (O(2)(•-)), which reacts with NO(•) in a diffusion-controlled process (k approximately 10(10) M(-1) s(-1)). The reactions of NO(•) with proteins containing iron-sulfur clusters ([FeS]) remain little studied and the reported rate constants of the first steps of these reactions are considerable (k approximately 10(5) M(-1) s(-1)). Not surprisingly, the interactions of proteins containing iron-sulfur clusters with NO(•) remain ambiguous and have been associated with both physiological and pathophysiological effects. Overall, it is emphasized that any claimed biological action of NO(•) should be connected with its interaction with kinetically relevant biotargets. Although reactivity toward biotargets is only one of the factors contributing to cellular and tissue responses mediated by short-lived species, such as NO(•) and other oxygen-derived species, it is a critical factor. Therefore, taking reactivity into account is important to advancing our knowledge on redox signaling mechanisms.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Toledo JC Jr,Augusto Odoi
10.1021/tx300042gsubject
Has Abstractpub_date
2012-05-21 00:00:00pages
975-89issue
5eissn
0893-228Xissn
1520-5010journal_volume
25pub_type
杂志文章,评审abstract::Thioureas are oxygenated by flavin-containing monooxygenases (FMOs), forming reactive sulfenic and/or sulfinic acids. Sulfenic acids can reversibly react with GSH and drive oxidative stress through a redox cycle. For this reason, thiourea S-oxygenation is an example of FMO-dependent bioactivation of a xenobiotic. Func...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx034253s
更新日期:2004-05-01 00:00:00
abstract::The trichothecene mycotoxin T-2 toxin, which is produced by fungi of the Fusarium species, is a worldwide occurring contaminant of cereal based food and feed. The cytotoxic properties of T-2 toxin are already well described with apoptosis being a major mechanism of action in various cell lines as well as in primary ce...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx3004664
更新日期:2013-03-18 00:00:00
abstract::3-Methylindole (3MI) is a preferential pneumotoxicant found in cigarette smoke. A number of lung-expressed human cytochrome P450 enzymes, including 1A1, 2F1, and 2A13, catalyze the metabolism of 3MI to reactive intermediates that fragment DNA, measured with the Comet assay to assess DNA damage, in a cytochrome P450-de...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx100147z
更新日期:2010-11-15 00:00:00
abstract::Free-radical oxidation of human plasma low-density lipoprotein (LDL) produces (carboxyalkyl)pyrrole (CAP) epitopes that were detected with enzyme-linked immunosorbent assays using antibodies raised against keyhole limpet hemocyanin (KLH)-bound 2-(omega-carboxyheptyl)-pyrrole (CHP) and 2-(omega-carboxypropyl)pyrrole (C...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx970112c
更新日期:1997-12-01 00:00:00
abstract::There is interest in the relative toxicities of emissions from electronic cigarettes and tobacco cigarettes. Lists of cigarette smoke priority toxicants have been developed to focus regulatory initiatives. However, a comprehensive assessment of e-cigarette chemical emissions including all tobacco smoke Harmful and Pot...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.6b00188
更新日期:2016-10-17 00:00:00
abstract::Arylamines (AAs) and heterocyclic aromatic amines (HAAs) are structurally related carcinogens formed during the combustion of tobacco or cooking of meat. They undergo cytochrome P450 mediated N-hydroxylation to form metabolites which bind to DNA and lead to mutations. The N-hydroxylated metabolites of many AAs also ca...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00418
更新日期:2016-03-21 00:00:00
abstract::The preparation and DNA binding characteristics of a structural analog of Hoechst 33258 bearing two pyridinic nitrogen atoms are described. The 1H NMR signals of the complex formed between the new ligand 1 and decadeoxyribonucleotide d(CATGGCCATG)2 were assigned by employing one- and two-dimensional NMR techniques. In...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00029a003
更新日期:1992-09-01 00:00:00
abstract::Bleomycin has a long-studied mechanism of action through the formation of a complex with metals, such as iron. The bleomycin-iron complex was recently shown to induce membrane damage by free radical reactivity. Because the use of Fe nanoparticles is spreading for drug delivery strategies, molecular mechanisms of cell ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.0c00162
更新日期:2020-10-19 00:00:00
abstract::The mechanism of formation of etheno (epsilon) adducts of nucleic acid bases from 2-haloacetaldehydes is generally assumed to occur via initial Schiff base formation resulting from reaction of the aldehyde with an exocyclic amine. We recently revised the 1H NMR assignments of the epsilon protons of 1,N2-epsilon-Guo (G...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00038a014
更新日期:1994-03-01 00:00:00
abstract::The oral dipeptidyl peptidase 1 (DPP1) inhibitor AZD5248 showed aortic binding in a rat quantitative whole-body autoradiography (QWBA) study, and its development was terminated prior to human dosing. A mechanistic hypothesis for this finding was established invoking reactivity with aldehydes involved in the cross-link...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.5b00236
更新日期:2015-10-19 00:00:00
abstract::Jay Amin hydroxamic acid (JAHA; N8-ferrocenylN1-hydroxy-octanediamide) is a ferrocene-containing analogue of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA). JAHA's cytotoxic activity on MDA-MB231 triple negative breast cancer (TNBC) cells at 72 h has been previously demonstrated with ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.7b00269
更新日期:2017-12-18 00:00:00
abstract::8-Oxo-2'-deoxyguanosine (OdG) is an abundant DNA lesion produced during oxidative damage to DNA. It can form relatively stable base pairs with both dC and dA that mimic natural dG:dC and dT:dA base pairs, respectively. Thus, when in the template strand, OdG can direct the insertion of either dCTP or dATP during replic...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx300365g
更新日期:2012-11-19 00:00:00
abstract::Epidemiological evidence suggests a lower incidence of Parkinson's disease in smokers than in nonsmokers. This evidence, together with the lower levels of brain monoamine oxidase (MAO) activity in smokers and the potential neuroprotective properties of MAO inhibitors, prompted studies which led to the isolation and ch...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx000224v
更新日期:2001-05-01 00:00:00
abstract::Iron (Fe) chelation therapy was initially designed to alleviate the toxic effects of excess Fe evident in Fe-overload diseases. However, the novel toxicological properties of some Fe chelator-metal complexes have shifted appreciable focus to their application in cancer chemotherapy. Redox-inactive Fe chelator complexe...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx700039c
更新日期:2007-05-01 00:00:00
abstract::Nickel(II) compounds are established human carcinogens, but the molecular mechanisms underlying their activity are only partially known. One mechanism may include mediation by nickel of promutagenic oxidative DNA damage that depends on Ni(II) binding to chromatin. To characterize such binding at the histone moiety of ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx00047a007
更新日期:1995-07-01 00:00:00
abstract::Recent reports by Galeazzi and co-workers demonstrated the susceptibility of Abeta(1-42) to undergo dityrosine formation via peroxidase-catalyzed tyrosine cross-linking. We have formed dityrosine cross-links in Abeta(1-40) using these enzymatic conditions as well as a copper-H(2)O(2) method. The efficiency of dityrosi...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx025666g
更新日期:2003-04-01 00:00:00
abstract::Epidemiological studies have implicated a role for airborne particulates of <2.5 microm diameter in the development/exacerbation of chronic cardiopulmonary disease; however, specific pathogenic mechanisms and the etiological significance of particle physicochemical properties remain unresolved. Using a microporous alu...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx049893p
更新日期:2004-10-01 00:00:00
abstract::The environmental contaminant benzo[c]phenanthrene (B[c]Ph) has weak carcinogenic activity in rodent bioassays; however, the fjord region diol epoxides of B[c]Ph, B[c]Ph-3,4-diol 1,2-epoxides (B[c]PhDE), are potent carcinogens. To determine the role of cytochrome P450 isozymes in the activation of B[c]Ph in MCF-7 cell...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx960174n
更新日期:1997-05-01 00:00:00
abstract::The chemical reactivity of styrene-7,8-oxide (SO), an alkylating agent with high affinity for the guanine–N7 position and a probable carcinogen for humans, with 4-(p-nitrobenzyl)pyridine (NBP), a trap for alkylating agents with nucleophilic characteristics similar to those of DNA bases, was investigated kinetically in...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx5002892
更新日期:2014-10-20 00:00:00
abstract::Ferroptosis is a form of cell death that requires phospholipid peroxidation and has attracted increased attention, both as a means to eradicate tumors resistant to standard chemotherapy and for its potential contribution to tissue damage such as in ischemia/reperfusion. The center stage taken by phospholipid peroxidat...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/acs.chemrestox.8b00349
更新日期:2019-03-18 00:00:00
abstract::Idiosyncratic drug reactions (IDRs) represent a major clinical problem, and at present, the mechanisms involved are still poorly understood. One animal model that we have used for mechanistic studies of IDRs is penicillamine-induced autoimmunity in Brown Norway (BN) rats. Previous work in our lab found that macrophage...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx900087z
更新日期:2009-07-01 00:00:00
abstract::Nuclear magnetic resonance (NMR) spectroscopy has traditionally been considered as an indispensable tool in elucidating structures of metabolites. With the advent of Fourier transform (FT) spectrometers, along with improvements in software and hardware (such as high-field magnets, cryoprobes, versatile pulse sequences...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx800251p
更新日期:2009-02-01 00:00:00
abstract::Among the cellular components that can react directly with peroxynitrite in the presence of physiological CO(2) concentrations are sulfur-, selenium-, and metal-containing proteins, in particular hemoproteins. We have previously shown that the reactions of peroxynitrite with oxymyoglobin (MbFeO(2)) and oxyhemoglobin p...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx025595l
更新日期:2003-03-01 00:00:00
abstract::The growth-promoting effects of estrogens in hormone-dependent tumor tissues involve receptor-mediated pathways that are well-recognized; however, the role of estrogens in tumor initiation remains controversial. Estrogen metabolites, primarily the catechol estrogens (CE's), have been implicated in tumor initiation via...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx980128i
更新日期:1999-03-01 00:00:00
abstract::All living organisms are exposed to xenobiotics from the environment. The exposure can lead to the formation of covalent adducts of xenobiotics or their metabolites with nucleic acids (NAs).The knowledge of NA adduct structure provides valuable information n the mechanism of carcinogenesis on a molecular level. While ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章,评审
doi:10.1021/tx5004535
更新日期:2015-02-16 00:00:00
abstract::To obtain definitive information about the mechanisms of urinary calculus formation and the structural characteristics of the calculi induced by biphenyl administration in rats, with a focus on the sex dependency, the constituents of the urinary calculi were analyzed by HPLC, inductively coupled plasma spectroscopy (I...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0000163
更新日期:2000-08-01 00:00:00
abstract::Chromium(III) tris(picolinate) [Cr(pic)3] is currently a very popular nutritional supplement; however, its safety has recently been questioned, especially with regard to its ability to act as a clastogen. At physiologically relevant concentrations, Cr(pic)3 is reduced by biological reductants, including ascorbate and ...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx9900167
更新日期:1999-06-01 00:00:00
abstract::The PI3K/Akt/mTOR pathway is considered to be an attractive target for the development of novel anticancer molecules. This paper reports for the first time that a small molecule, antrocin (MW = 234), from Antrodia camphorata was a potent antagonist in various cancer types, being highest in metastatic breast cancer MDA...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx100318m
更新日期:2011-02-18 00:00:00
abstract::Topoisomerase II is an essential nuclear enzyme involved in regulating DNA topology to facilitate replication and cell division. Disruption of topoisomerase II function by chemotherapeutic agents is in use as an effective strategy to fight cancer. Etoposide is an anticancer therapeutic that disrupts the catalytic cycl...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/acs.chemrestox.6b00209
更新日期:2016-09-19 00:00:00
abstract::The toxic alpha,beta-unsaturated aldehyde acrolein readily attacks proteins, generating adducts at cysteine, histidine, and lysine residues. In this study, rabbit antiserum was raised against acrolein-modified keyhole limpet hemocyanin in the expectation that it would allow immunodetection of adducted proteins in biol...
journal_title:Chemical research in toxicology
pub_type: 杂志文章
doi:10.1021/tx0341106
更新日期:2003-10-01 00:00:00