Nitroxide antioxidant as a potential strategy to attenuate the oxidative/nitrosative stress induced by hydrogen peroxide plus nitric oxide in cultured neurons

Lee, Ching-Tien; Yu, Liang-En; Wang, Jiz-Yuh

doi:10.1016/j.niox.2016.02.001

Cited by 27 publications

(12 citation statements)

References 55 publications

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“…The MAPK signaling pathway is involved in modulation of various physiological and pathological events. The correlation of the MAPK signaling pathway with ROS has been investigated in many studies (Ramos-Nino et al, 2002 ; Cakir and Ballinger, 2005 ; Batra et al, 2012 ; Lee et al, 2016 ). The MAPK pathway comprises extra-cellular signal-regulated kinases (ERK 1/2), the p38 kinase, and the stress-activated protein kinase or c-Jun N-terminal kinase (SAPK/JNK) (Seger and Krebs, 1995 ).…”

Section: Resultsmentioning

confidence: 99%

Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling-Induced Cognitive Impairment and Depressive-Like Behavior

Zhu

Dong

Han

et al. 2017

Front. Behav. Neurosci.

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Epilepsy is a chronic neurological disease which is usually associated with psychiatric comorbidities. Depsression and cognition impairment are considered to be the most common psychiatric comorbidities in epilepsy patients. However, the specific contribution of epilepsy made to these psychiatric comorbidities remains largely unknown. Here we use pentylenetetrazole (PTZ) kindling, a chronic epilepsy model, to identify neuronal nitric oxide synthase (nNOS) as a signaling molecule triggering PTZ kindling-induced cognitive impairment and depressive-like behavior. Furthermore, we identified that both hippocampal MAPK and PI3K/AKT signaling pathways were activated in response to PTZ kindling, and the increased MAPK and PI3K/AKT signaling activation was paralleled by increased level of reactive oxygen species (ROS) in the hippocampus. However, the PTZ kindling-induced MAPK, PI3K/AKT signaling activities and the ROS level were attenuated by nNOS gene deficiency, suggesting that nNOS may act through ROS-mediated MAPK and PI3K/AKT signaling pathways to trigger cognition deficit and depressive-like behavior in PTZ-kindled mice. Our findings thus define a specific mechanism for chronic epilepsy-induced cognitive impairment and depressive-like behavior, and identify a potential therapeutic target for psychiatric comorbidities in chronic epilepsy patients.

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Section: Resultsmentioning

confidence: 99%

Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling-Induced Cognitive Impairment and Depressive-Like Behavior

Zhu

Dong

Han

et al. 2017

Front. Behav. Neurosci.

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“…Concurrent stimulation of superoxide by α‐synuclein increases production of ONOO−. Lee and colleagues tested several antioxidants, including superoxide dismutase, catalase, 2,2,6,6‐tetramethyl‐1‐piperidinoxyl (TEMPO), NAC, dimethylthiourea and uric acid in preventing protein tyrosine nitration caused by ROS and NO in primary neuronal cultures (Lee et al ., ). Of these, TEMPO was the most effective at promoting clearance of ROS/RNS and inhibition of stress signalling pathways.…”

Section: Reactive Nitrogen Species As a Therapeutic Target In Neurodementioning

confidence: 97%

“…NO‐mediated S ‐nitrosylation (the chemical reaction is S ‐nitrosation, but the ‘ylation’ suffix is commonly used in biology) entails the addition or transfer of a nitroso group to a free sulphydryl group in a protein, forming S ‐nitrosocysteine. This happens as part of normal cellular signalling, but dysregulation of S ‐nitrosylation (termed ‘nitrosative stress’) is being increasingly linked to human neurodegenerative disorders (Chung, ; Cobb and Cole, ; Lee et al ., ).…”

Section: Reactive Nitrogen Species As a Therapeutic Target In Neurodementioning

confidence: 99%

Redox‐based therapeutics in neurodegenerative disease

McBean

López

Wallner

2016

British J Pharmacology

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This review describes recent developments in the search for effective therapeutic agents that target redox homeostasis in neurodegenerative disease. The disruption to thiol redox homeostasis in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and multiple sclerosis is discussed, together with the experimental strategies that are aimed at preventing, or at least minimizing, oxidative damage in these diseases. Particular attention is given to the potential of increasing antioxidant capacity by targeting the Nrf2 pathway, the development of inhibitors of NADPH oxidases that are likely candidates for clinical use, together with strategies to reduce nitrosative stress and mitochondrial dysfunction. We describe the shortcomings of compounds that hinder their progression to the clinic and evaluate likely avenues for future research. LINKED ARTICLESThis article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc Abbreviations 6(OH)DA, 6-hydroxydopamine; AD, Alzheimer's disease; ADME(T), absorption, distribution, metabolism and excretion/toxicity; ALS, amyotrophic lateral sclerosis; APP, amyloid precursor protein; ARE, antioxidant response element; ASSNAC, S-allylmercapto-N-acetyl cysteine; Aβ, amyloid-β; CA, carnosic acid; DMF, dimethylfumarate; EAE, experimental autoimmune encephalomyelitis; EpRE, electrophile response element; GCL, glutamate cysteine ligase; GR, glutathione reductase; Grx, glutaredoxin; GSK-3β, glycogen synthase kinase-3β; Keap1, Kelch-like ECH-associated protein-1; MMF, monomethylfumarate; MPTP, 1-methyl, 4-phenyl-1,2,3,6-tetrahydropyridine; MS, multiple sclerosis; MPO, myeloperoxidase; NAC, N-acetylcysteine; NACA, N-acetylcysteine amide; NOX, NADPH oxidase; NQO1, NAD(P)H quinone oxidoreductase-1; Nrf2, nuclear factor (erythroid-derived 2)-like 2; PD, Parkinson's disease; PS1, pre-senelin-1; RNS, reactive nitrogen species; SN, substantia nigra; Trx, thioredoxin; TrxR, thioredoxin reductase; xCT, functional subunit of the x c À exchanger Disruption of cerebral redox homeostasis is a common occurrence in a range of human neurodegenerative disorders, and although much is understood of mechanistic dysfunction, the gap between knowledge and the availability of effective therapies remains wide. In this review, we focus on the potential for developing therapeutic agents that promote the availability of thiol redox antioxidants or boost the antioxidant capacity of cells via stimulation of the transcription factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In addition, we discuss options for reducing ROS production by inhibition of NADPH oxidases (NOXs), limiting nitrative stress or targeting mitochondrial dysfunction. Other potential strategies for limiting oxidative stress in neurodegenerative disease include nutrient and vitamin supplementation and metal chelators, which are excluded from the discussion. These approaches are t...

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“…182,184 In culture primary neurons, TEMPO comprehensively and efficaciously decreased H 2 O 2 plus S-nitroso-N-acetyl-D,L-penicillamine-evoked activation of stress cascades of p38 MAPK and p53, production of • NO, ROS, and ONOO-, double-strand breaks of DNA, and nitration of protein tyrosine residues. 185 Moreover, TEMPOL displayed outstanding antioxidant activity in both cultured rabbit lens epithelial cells treated with H 2 O 2 186 and 6-OHDA-challenged MN9D dopaminergic mesencephalic cells. 187 Similar effects have been shown in a mouse model of autonomic dysfunction in Parkinson's disease.…”

Section: Nitroxidesmentioning

confidence: 97%

“…For instance, TEMPO has shown protective properties in radiation‐induced damage and I/R injury . In culture primary neurons, TEMPO comprehensively and efficaciously decreased H 2 O 2 plus S ‐nitroso‐ N ‐acetyl‐ d , l ‐penicillamine‐evoked activation of stress cascades of p38 MAPK and p53, production of • NO, ROS, and ONOO‐, double‐strand breaks of DNA, and nitration of protein tyrosine residues . Moreover, TEMPOL displayed outstanding antioxidant activity in both cultured rabbit lens epithelial cells treated with H 2 O 2 and 6‐OHDA‐challenged MN9D dopaminergic mesencephalic cells .…”

Section: Nitroxidesmentioning

confidence: 99%

NO and HNO donors, nitrones, and nitroxides: Past, present, and future

Oliveira

Benfeito

Fernandes

et al. 2017

Medicinal Research Reviews

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The biological effects attributed to nitric oxide ( NO) and nitroxyl (HNO) have been extensively studied, propelling their array of putative clinical applications beyond cardiovascular disorders toward other age-related diseases, like cancer and neurodegenerative diseases. In this context, the unique properties and reactivity of the N-O bond enabled the development of several classes of compounds with potential clinical interest, among which NO and HNO donors, nitrones, and nitroxides are of particular importance. Although primarily studied for their application as cardioprotective agents and/or molecular probes for radical detection, continuous efforts have unveiled a wide range of pharmacological activities and, ultimately, therapeutic applications. These efforts are of particular significance for diseases in which oxidative stress plays a key pathogenic role, as shown by a growing volume of in vitro and in vivo preclinical data. Although in its early stages, these efforts may provide valuable guidelines for the development of new and effective N-O-based drugs for age-related disorders. In this report, we review recent advances in the chemistry of NO and HNO donors, nitrones, and nitroxides and discuss its pharmacological significance and potential therapeutic application.

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Nitroxide antioxidant as a potential strategy to attenuate the oxidative/nitrosative stress induced by hydrogen peroxide plus nitric oxide in cultured neurons

Cited by 27 publications

References 55 publications

Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling-Induced Cognitive Impairment and Depressive-Like Behavior

Neuronal Nitric Oxide Synthase Contributes to PTZ Kindling-Induced Cognitive Impairment and Depressive-Like Behavior

Redox‐based therapeutics in neurodegenerative disease

NO and HNO donors, nitrones, and nitroxides: Past, present, and future

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