Chemical reactivity and biological effects of superoxide radicals

Chuaqui, Claudio; Petkau, A.

doi:10.1016/1359-0197(87)90105-6

Cited by 5 publications

(4 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Excess mitochondrial O2 •- levels can initiate a cascade of reactions leading to the generation of other forms of ROS (Chuaqui and Petkau, 1987), which can be even more detrimental to functioning of mitochondria. A side effect is depolarization of the mitochondrial membrane, resulting in an increase in intracellular ROS.…”

Section: Resultsmentioning

confidence: 99%

Diffusible Factors Secreted by Glioblastoma and Medulloblastoma Cells Induce Oxidative Stress in Bystander Neural Stem Progenitors

et al. 2016

View full text Add to dashboard Cite

Harmful effects that alter the homeostasis of neural stem or progenitor cells (NSPs) can affect regenerative processes in the central nervous system. We investigated the effect of soluble factors secreted by control or 137Cs-γ-irradiated glioblastoma or medulloblastoma cells on redox-modulated endpoints in recipient human NSPs. Growth medium harvested from the nonirradiated brain tumor cells, following 24 h of growth, induced prominent oxidative stress in recipient NSPs as judged by overall increases in mitochondrial superoxide radical levels (p < .001), activation of c-jun N-terminal kinase, and decrease in the active form of FoxO3a. The induced oxidative stress was associated with phosphorylation of p53 on serine 15, a marker of DNA damage, induction of the cyclin-cyclin dependent kinase inhibitors p21Waf1 and p27Kip1, and perturbations in cell cycle progression (p < .001). These changes were also associated with increased apoptosis as determined by enhanced annexin V staining (p < .001) and caspase 8 activation (p < .05) and altered expression of critical regulators of self-renewal, proliferation, and differentiation. Exposure of the tumor cells to radiation only slightly altered the induced oxidative changes in the bystander NSPs, except for medium from irradiated medulloblastoma cells that was more potent at inducing apoptosis in the NSPs than medium from nonirradiated cells (p < .001). The elucidation of such stressful bystander effects provides avenues to understand the biochemical events underlying the development or exacerbation of degenerative outcomes associated with brain cancers. It is also relevant to tissue culture protocols whereby growth medium conditioned by tumor cells is often used to support the growth of stem cells.

show abstract

Section: Resultsmentioning

confidence: 99%

Diffusible Factors Secreted by Glioblastoma and Medulloblastoma Cells Induce Oxidative Stress in Bystander Neural Stem Progenitors

et al. 2016

View full text Add to dashboard Cite

show abstract

“…These rate constants require that the time for half the 02-to disappear by dismutation varies from milliseconds to hours depending upon concentrations (nM to mM) and pH (Pry 9 1986). The whole chemistry of 02 -should be seen from two aspects: (i) O~ being the reactant or intermediate in processes that could be deleterious to the living ceils (Table I) (Bielski and Cabelli, 1991;Chiaqui and Petkau, 1987;Czapski et al, 1988;Liochev and Fridovich, 1994;Winterbourn, 1993); and (ii) 02 being a "biological control", defined as a "second messenger" (Saran and Bors, 1989;Suzuki et al, 1997). Notably, among the cellular compounds susceptible to free radical chain oxidation initiated by 02 are sulfites, dihydroflavins and catecholamines.…”

Section: Ros and Rns In Neurologic Disorders 203mentioning

confidence: 99%

“…Generally there are two mechanistic ways of O 2 formation in vivo: (i) "radical leakage" in mitochondria, in the course of four electron reduction of 02 to H20 (reactions 1-4) where two formal states -O~-and O 3-possess radical character; (ii) "electron leakage" -oneelectron process which is usually occurring in the metabolism of xenobiotics (Metodiewa and Dunford, 1993;Saran and Bors, 1990). The chemical reactivity of (O~) (Allen and Bielski, 1982;Bielski et al, 1985;Chiaqui and Petkau, 1987;Fee and Valentine, 1977) is conditioned by its unpaired ("odd") electron and negative charge: it is principally a free oxygen radical, a nucleophile and complexing agent as well. The prominent feature of O~ is its ability to act as Br6nsted base by which in aqueous media, the acid-base equilibrium (pK~ =4.8) is shifted to form hydroperoxyl radical (HO~)…”

Section: Superoxide Anion Radical (02-)mentioning

confidence: 99%

Reactive oxygen species and reactive nitrogen species: Relevance to cyto(neuro)toxic events and neurologic disorders. An overview

1999

View full text Add to dashboard Cite

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are formed under physiological conditions in the human body and are removed by cellular antioxidant defense systems. During oxidative stress their increased formation leads to tissue damage and cell death. This process may be especially important in the central nervous system (CNS) which is vulnerable to ROS and RNS damage as the result of high 02 consumption, high lipid content and the relatively low antioxidant defenses in brain, compared with other tissues.Recently there has been an increased number of reports suggesting the involvement of free radicals and their non-radical derivatives in a variety of pathological events and multistage disorders including neurotoxicity, apoptotic death of neurons, and neural disorders: Alzheimer's (AD), Parkinson's disease (PD) and schizophrenia. Taking into consideration the basic molecular chemistry of ROS and RNS, their overall generation and location, in order to control or supress their action it is essential to understand the fundamental aspects of this problem. In this presentation we review and summarize the basics of all the recently known and important properties, mechanisms, molecular targets, possible involvement in cellular (neural) degeneration and apoptotic death and in pathogenesis of AD, PD and schizophrenia.The aim of this article is to provide an overview of our current knowledge of this problem and to inspire experimental strategies for the evaluation of optimum innovative therapeutic trials. Another purpose of this work is to shed some light on one of the most exciting recent advances in our understanding of the CNS: the realisation that RNS pathway is highly relevant to normal brain metabolism and to neurologic disorders as well. The interactions of RNS and ROS, their interconversions and the ratio of RNS/ ROS could be an important neural tissue injury mechanism(s) involved into etiology and pathogenesis of AD, PD and schizophrenia.It might be possible to direct therapeutic efforts at oxidative events in the pathway of neuronal degeneration and apoptotic death. From reviewed data, no single substance can be recommended for use in human studies. Some of the recent therapeutic strategies and neuroprotective trials need further development particularly those of antioxidants enhancement. Such an approach should also consider using combinations of radical(s) scavengers rather than a single substance.

show abstract

“…DNA damage induced by oxygen radicals creates a number of abnormal lesions and appears to play an important role in mutagenesis, carcinogenesis, and aging (1)(2)(3)(4)(5)(6). In particular, 8-hydroxy-2,-deoxyguanosine (8-OH-dG)2,3 has received considerable attention in recent years (7) as a consequence of its demonstrated mutagenic potential (Chart I) (8).…”

Section: Introductionmentioning

confidence: 99%

Nitrogen-15 nuclear magnetic resonance studies on the tautomerism of 8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine, and other C8-substituted guanine nucleosides

Cho¹,

Kadlubar²,

Culp³

et al. 1990

Chem. Res. Toxicol.

View full text Add to dashboard Cite

The favored tautomeric and ionic structures were examined for the oxidative DNA damage adduct 8-hydroxy-2'-deoxyguanosine and its RNA analogue 8-hydroxyguanosine by 15N NMR spectroscopy. In addition, 15N chemical shifts and coupling constants from 13 different guanine nucleosides, including a wide variety of C8 substitutions (OH, SH, Br, OCH2C6H5, OCH3, SCH3, and SO2CH3), have been analyzed with respect to their tautomeric structures. A -98.5-Hz proton-nitrogen coupling constant observed for the N7 resonance of 8-hydroxyguanosine in dimethyl sulfoxide was evidence for 8-keto substitution, which is contrary to the structure implied by the generally used nomenclature. The pH dependence of 15N NMR spectra of 8-hydroxyguanosine in aqueous solution showed downfield shifts of the N1 and N7 resonances that were greater than 50 ppm, which indicated the conversion from a neutral 6,8-diketo to a 6-enolate-8-keto (pKa1 = 8.6) and finally to a 6,8-dienolate structure (pKa2 = 11.7). There was no evidence of an 8-enol substituent in the absence of ionization. It is proposed that the syn conformation of these oxidized bases in duplex DNA and RNA can be further stabilized by abnormal hydrogen bonding or mispairing that involves N7-H. The combined data show that 15N NMR is a sensitive probe to examine tautomerism of the guanine ring system. The analysis indicates that the change from a single to a double bond for the C8 substituent, and the accompanying removal of the normal double bond between N7 and C8 on the imidazole ring system, has no detectable effect on the tautomerism at the N1-O6 site of the pyrimidine ring system for both the 8-keto and 8-thio substitutions. In addition, large differences in electronegativity of the C8 substituents do not alter the N1-O6 tautomerism.

show abstract

Chemical reactivity and biological effects of superoxide radicals

Cited by 5 publications

References 56 publications

Diffusible Factors Secreted by Glioblastoma and Medulloblastoma Cells Induce Oxidative Stress in Bystander Neural Stem Progenitors

Diffusible Factors Secreted by Glioblastoma and Medulloblastoma Cells Induce Oxidative Stress in Bystander Neural Stem Progenitors

Reactive oxygen species and reactive nitrogen species: Relevance to cyto(neuro)toxic events and neurologic disorders. An overview

Nitrogen-15 nuclear magnetic resonance studies on the tautomerism of 8-hydroxy-2'-deoxyguanosine, 8-hydroxyguanosine, and other C8-substituted guanine nucleosides

Contact Info

Product

Resources

About