4-Hydroxy-2-nonenal: a product and mediator of oxidative stress

Uchida, Koji

doi:10.1016/s0163-7827(03)00014-6

Cited by 1,051 publications

(933 citation statements)

References 128 publications

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“…To further examine the mechanism of GGT mRNA V-2 induction by HNE, we first determined its expression pattern in response to HNE. The physiological concentration of HNE in the plasma is reported to be less than 1 µM [23,39], but its concentration can reach as high as 10 µM to 5 mM in plasma membrane under conditions of oxidative stress [40,41]. HNE concentrations used in this study were between 5 and 20 µM.…”

Section: Increase Of Ggt Mrna V-2 By Hne In L2 Cellsmentioning

confidence: 87%

“…Based on the evidence that GGT mRNA V-2 is abundant in the lung and that the induction of mRNA V-2 is through EpRE, it can be inferred that EpRE/Nrf2 signaling is at least partially involved in GGT induction by other oxidative stress generators, including the redox-cycling quinones [11][12][13][14], NO 2 [10], and hyperoxia [15]. Because every investigated type of oxidative stress results in increased HNE production [41,88], the underlying mechanism of GGT induction by these agents likely involves the production of the common inducer HNE.…”

Section: Discussionmentioning

confidence: 99%

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γ-Glutamyl transpeptidase is induced by 4-hydroxynonenal via EpRE/Nrf2 signaling in rat epithelial type II cells

Zhang

Liu

Dickinson

et al. 2006

Free Radical Biology and Medicine

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Abstractγ-Glutamyl transpeptidase (GGT) plays key roles in glutathione homeostasis and metabolism of glutathione S-conjugates. Rat GGT is transcribed via five tandemly arranged promoters into seven transcripts. The transcription of mRNAV is controlled by promoter 5. Previously we found that GGT mRNAV-2 was responsible for the induction of GGT in rat alveolar epithelial cells by 4-hydroxynonenal (HNE). In the current study, the underlying mechanism was investigated. Reporter deletion and mutation analysis demonstrated that an electrophile-response element (EpRE) in the proximal region of GGT promoter 5 (GP5) was responsible for the basal-and HNE-induced promoter activity. Gel-shift assays showed an increased binding activity of GP5 EpRE after HNE exposure. The nuclear content of NF-E2-related factor 2 (Nrf2) was significantly increased by HNE. The recruitment of Nrf2 to GP5 EpRE after HNE treatment was demonstrated by supershift and chromatin immunoprecipitation assays. The tissue expression pattern of GGT mRNA V was previously unknown. Using polymerase chain reaction, we found that GGT mRNAV-2 was expressed in many tissues in rat. Taken together, GGT mRNAV-2 is widely expressed in rat tissues and its basal and HNE-induced expression is mediated through EpRE/Nrf2 signaling.

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Section: Increase Of Ggt Mrna V-2 By Hne In L2 Cellsmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

γ-Glutamyl transpeptidase is induced by 4-hydroxynonenal via EpRE/Nrf2 signaling in rat epithelial type II cells

Zhang

Liu

Dickinson

et al. 2006

Free Radical Biology and Medicine

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“…The physiological concentration of HNE in the plasma is reportedly from 0.3-0.7 μM (164,165) but its concentration can reach as high 10 μM or more in plasma membrane under conditions of oxidative stress (166,167). While HNE is therefore considered as a biomarker of oxidative stress (167,168), it is also implicated in various oxidative stress-related diseases, including atherosclerosis (169), neurodegenerative diseases (170), and fibrosis (171).…”

Section: A Hne: Production Reaction and Eliminationmentioning

confidence: 99%

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

Forman

Fukuto

Miller

et al. 2008

Archives of Biochemistry and Biophysics

219

165

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During the past several years, major advances have been made in understanding how reactive oxygen species (ROS) and nitrogen species (RNS) participate in signal transduction. Identification of the specific targets and the chemical reactions involved still remains to be resolved with many of the signaling pathways in which the involvement of reactive species has been determined. Our understanding is that ROS and RNS have second messenger roles. While cysteine residues in the thiolate (ionized) form found in several classes of signaling proteins can be specific targets for reaction with H 2 O 2 and RNS, better understanding of the chemistry, particularly kinetics, suggests that for many signaling events in which ROS and RNS participate, enzymatic catalysis is more likely to be involved than non-enzymatic reaction. Due to increased interest in how oxidation products, particularly lipid peroxidation products, also are involved with signaling, a review of signaling by 4-hydroxy-2-nonenal (HNE) is included. This article focuses on the chemistry of signaling by ROS, RNS, and HNE and will describe reactions with selected target proteins as representatives of the mechanisms rather attempt to comprehensively review the many signaling pathways in which the reactive species are involved. Keywords signaling; glutathione; thioredoxin; oxidants; reactive oxygen species; thiols; peroxide; nitric oxide; peroxynitrite; 4-hydroxynonenal; cysteine; hydrogen peroxide; protein tyrosine phosphatase; reactive nitrogen species; eNOS; iNOS; nNOS; soluble guanylate cyclase; cGMP; tyrosine nitration; fatty acid nitration; NO-heme; NO-metal complexes; nitrite; protein kinase C; ERK; JNK; p38MAPK; tyrosine kinase receptors; calcium OVERVIEW OF SIGNALING BY REACTIVE SPECIESUnderstanding of the roles of reactive oxygen species (ROS), reactive nitrogen species (RNS) and the lipid peroxidation product, 4-hydroxy-2-nonenal (HNE) in signaling has evolved rapidly during the last decade. This has been markedly helped by identification of the specific targets in signaling pathways. In previous reviews, we defined how ROS, H 2 O 2 in particular,

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“…10 While the molecular mechanisms of 4-HNE mitochondrial toxicity still remain unclear, it has been observed demonstrated that the generation of additional ROS and additional LP initiation is involved in the mechanism(s) of 4-HNE-induced neurotoxicity. 26,27 Whatever the intricacies of 4-HNE neurotoxicity are, the loss of mitochondrial integrity is the pivotal event leading to neuronal cell death in the ischemic penumbra in stroke models 13 and in models of acute neurological injury including TBI 1,28 and spinal cord injury. 29,30 Our in vitro data demonstrate protective effects of PZ against 4-HNE-induced bioenergetic function and oxidative damage in isolated mitochondria that tracks with a decrease in 4-HNE modification of mitochondrial proteins.…”

Section: Discussionmentioning

confidence: 99%

Phenelzine Mitochondrial Functional Preservation and Neuroprotection after Traumatic Brain Injury Related to Scavenging of the Lipid Peroxidation-Derived Aldehyde 4-Hydroxy-2-Nonenal

Singh

Gilmer

Miller

et al. 2013

J Cereb Blood Flow Metab

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Phenelzine (PZ) is a scavenger of the lipid peroxidation (LP)-derived reactive aldehyde 4-hydroxynonenal (4-HNE) due to its hydrazine functional group, which can covalently react with 4-HNE. In this study, we first examined the ability of PZ to prevent the respiratory depressant effects of 4-HNE on normal isolated brain cortical mitochondria. Second, in rats subjected to controlled cortical impact traumatic brain injury (CCI-TBI), we evaluated PZ (10 mg/kg subcutaneously at 15 minutes after CCI-TBI) to attenuate 3-hour post-TBI mitochondrial respiratory dysfunction, and in separate animals, to improve cortical tissue sparing at 14 days. While 4-HNE exposure inhibited mitochondrial complex I and II respiration in a concentration-dependent manner, pretreatment with equimolar concentrations of PZ antagonized these effects. Western blot analysis demonstrated a PZ decrease in 4-HNE in mitochondrial proteins. Mitochondria isolated from peri-contusional brain tissue of CCI-TBI rats treated with vehicle at 15 minutes after injury showed a 37% decrease in the respiratory control ratio (RCR) relative to noninjured mitochondria. In PZ-treated rats, RCR suppression was prevented (Po0.05 versus vehicle). In another cohort, PZ administration increased spared cortical tissue from 86% to 97% (Po0.03). These results suggest that PZ's neuroprotective effect is due to mitochondrial protection by scavenging of LP-derived 4-HNE.

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4-Hydroxy-2-nonenal: a product and mediator of oxidative stress

Cited by 1,051 publications

References 128 publications

γ-Glutamyl transpeptidase is induced by 4-hydroxynonenal via EpRE/Nrf2 signaling in rat epithelial type II cells

γ-Glutamyl transpeptidase is induced by 4-hydroxynonenal via EpRE/Nrf2 signaling in rat epithelial type II cells

The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

Phenelzine Mitochondrial Functional Preservation and Neuroprotection after Traumatic Brain Injury Related to Scavenging of the Lipid Peroxidation-Derived Aldehyde 4-Hydroxy-2-Nonenal

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