Inhibition of the oxidative metabolism of 3,4-dihydroxyphenylacetaldehyde, a reactive intermediate of dopamine metabolism, by 4-hydroxy-2-nonenal

Florang, Virginia R.; Rees, Jennifer; Brogden, Nicole K.; Anderson, David G.; Hurley, Thomas D.; Doorn, Jonathan A.

doi:10.1016/j.neuro.2006.07.018

Cited by 59 publications

(74 citation statements)

References 35 publications

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“…Here we observed a quite potent inhibition of purified ALDH-2 by 10 M 4HNE, which is in accordance with previously published data (25). Because the reducing cofactor DTT did not significantly improve this inhibitory effect, we suggest irreversible inhibition of ALDH-2 by 4HNE.…”

Section: Discussionsupporting

confidence: 93%

Regulation of Human Mitochondrial Aldehyde Dehydrogenase (ALDH-2) Activity by Electrophiles in Vitro

Oelze¹,

Knorr²,

Schell³

et al. 2011

Journal of Biological Chemistry

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Recently, mitochondrial aldehyde dehydrogenase (ALDH-2) was reported to reduce ischemic damage in an experimental myocardial infarction model. ALDH-2 activity is redox-sensitive. Therefore, we here compared effects of various electrophiles (organic nitrates, reactive fatty acid metabolites, or oxidants) on the activity of ALDH-2 with special emphasis on organic nitrate-induced inactivation of the enzyme, the biochemical correlate of nitrate tolerance. Recombinant human ALDH-2 was overexpressed in Escherichia coli; activity was determined with an HPLC-based assay, and reactive oxygen and nitrogen species formation was determined by chemiluminescence, fluorescence, protein tyrosine nitration, and diaminonaphthalene nitrosation. The organic nitrate glyceryl trinitrate caused a severe concentration-dependent decrease in enzyme activity, whereas incubation with pentaerythritol tetranitrate had only minor effects. 4-Hydroxynonenal, an oxidized prostaglandin J 2 , and 9-or 10-nitrooleate caused a significant inhibition of ALDH-2 activity, which was improved in the presence of Mg 2؉ and Ca 2؉ . Hydrogen peroxide and NO generation caused only minor inhibition of ALDH-2 activity, whereas peroxynitrite generation or bolus additions lead to severe impairment of the enzymatic activity, which was prevented by the thioredoxin/ thioredoxin reductase (Trx/TrxR) system. In the presence of glyceryl trinitrate and to a lesser extent pentaerythritol tetranitrate, ALDH-2 may be switched to a peroxynitrite synthase. Electrophiles of different nature potently regulate the enzymatic activity of ALDH-2 and thereby may influence the resistance to ischemic damage in response to myocardial infarction. The Trx/TrxR system may play an important role in this process because it not only prevents inhibition of ALDH-2 but is also inhibited by the ALDH-2 substrate 4-hydroxynonenal. Aldehyde dehydrogenases (ALDH)3 contribute to detoxification of toxic aldehydes. The mitochondrial isoform (ALDH-2) is a major sink for acetaldehyde formed from ethanol metabolism, and the East Asian variant (ALDH2*2, E504K) is responsible for alcohol intolerance in a large part of the East Asian population (1). In 2002, Chen et al. (2) identified the ALDH-2 as an organic nitrate reductase, important for the bioactivation of nitroglycerin (glyceryl trinitrate (GTN)), and thereby identified the yet unknown "enzyme receptor" for the vasodilatory action of GTN. The role of ALDH-2 for GTN bioactivation and development of nitrate tolerance was confirmed in animal experimental (3) and human studies (4). A proof at the molecular level was provided using ALDH-2 Ϫ/Ϫ mice showing impaired GTN potency but normal responses to the NO donor sodium nitroprusside and isosorbide dinitrate (5). This finding was extended by demonstrating in ALDH-2 Ϫ/Ϫ mice that pentaerythritol tetranitrate (PETN) and its trinitrate metabolite (PETriN) but not the di-and mononitrate metabolites (PEDN and PEMN) are bioactivated by ALDH-2 (6). Mechanistic studies on ALDH-2 inactivation revealed that reactiv...

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Section: Discussionsupporting

confidence: 93%

Regulation of Human Mitochondrial Aldehyde Dehydrogenase (ALDH-2) Activity by Electrophiles in Vitro

Oelze¹,

Knorr²,

Schell³

et al. 2011

Journal of Biological Chemistry

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“…Research suggests that 4HNE and ACR (2-propenal), the most toxic byproducts of lipid peroxidation, are involved in the pathogenesis of neurodegenerative diseases [32] and traumatic nerve injury [33]. 4HNE, one of the 4-hydroxyalkenals generated from hydroxyperoxides, can bind to histidine, lysine, and cysteine residues of various proteins, thereby altering the protein structure and function.…”

Section: Mg Is a Potent Inducer Of Cell Death In Ims32 Whereas High mentioning

confidence: 99%

Differential Effects of High Glucose and Methylglyoxal on Viability and Polyol Metabolism in Immortalized Adult Mouse Schwann Cells

Sango¹,

Yanagisawa²,

Kato³

et al. 2008

TODIAJ

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Cultured Schwann cells under exposure to high glucose and methylglyoxal (MG) have been individually employed for studying diabetic neuropathy; however, similarities and differences between these two culture models have not been studied. We investigated the effects of high glucose and MG on viability, polyol pathway activity, and expression of oxidative stress markers (4-hydroxy-2-nonenal (4HNE), acrolein (ACR), and hexanoyl lysine (HEL)) in immortalized adult mouse Schwann cells (IMS32 cell line) in culture. Western blot and immunocytochemical analyses revealed that expression of aldose reductase (AR), 4HNE, ACR, and HEL in IMS32 was induced by exposure to both high glucose (30 mM) and MG (0.5 mM) for 48 h. Treatment with MG (0.1, 0.2, and 0.5 mM) induced cell death in a concentrationdependent manner, whereas high glucose environments (30 mM and 56 mM) did not impair cell viability. In contrast, intracellular sorbitol and fructose levels were significantly increased by high glucose, but not by MG. Taking these findings together, IMS32 cell line under high glucose conditions appears to be useful for studying oxidative stress in relation to the polyol pathway hyperactivity in diabetes. MG is capable of causing more detrimental damage to IMS32 than high glucose, but MG-induced upregulation of AR is unlikely to accelerate the polyol pathway activity.

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“…The peak area was then converted to concentration by comparison to a standard curve calculated from metabolite standards as previously described. 30,37–39 For the DA-supplemented metabolism experiments, cells were supplemented with 100 μ M DA 15 min prior to dieldrin treatment to initiate DA metabolism.…”

Section: Methodsmentioning

confidence: 99%

Cellular Localization of Dieldrin and Structure–Activity Relationship of Dieldrin Analogues in Dopaminergic Cells

Allen

Florang

Davenport

et al. 2013

Chem. Res. Toxicol.

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The incidence of Parkinson’s disease (PD) correlates with environmental exposure to pesticides, such as the organochlorine insecticide, dieldrin. Previous studies found an increased concentration of the pesticide in the striatal region of the brains of PD patients and also that dieldrin adversely affects cellular processes associated with PD. These processes include mitochondrial function and reactive oxygen species production. However, the mechanism and specific cellular targets responsible for dieldrin-mediated cellular dysfunction and the structural components of dieldrin contributing to its toxicity (toxicophore) have not been fully defined. In order to identify the toxicophore of dieldrin, a structure–activity approach was used, with the toxicity profiles of numerous analogues of dieldrin (including aldrin, endrin, and cis-aldrin diol) assessed in PC6-3 cells. The MTT and lactate dehydrogenase (LDH) assays were used to monitor cell viability and membrane permeability after treatment with each compound. Cellular assays monitoring ROS production and extracellular dopamine metabolite levels were also used. Structure and stereochemistry for dieldrin were found to be very important for toxicity and other end points measured. Small changes in structure for dieldrin (e.g., comparison to the stereoisomer endrin) yielded significant differences in toxicity. Interestingly, the cis-diol metabolite of dieldrin was found to be significantly more toxic than the parent compound. Disruption of dopamine catabolism yielded elevated levels of the neurotoxin, 3,4-dihydroxyphenylacetaldehyde, for many organochlorines. Comparisons of the toxicity profiles for each dieldrin analogue indicated a structure-specific effect important for elucidating the mechanisms of dieldrin neurotoxicity.

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Inhibition of the oxidative metabolism of 3,4-dihydroxyphenylacetaldehyde, a reactive intermediate of dopamine metabolism, by 4-hydroxy-2-nonenal

Cited by 59 publications

References 35 publications

Regulation of Human Mitochondrial Aldehyde Dehydrogenase (ALDH-2) Activity by Electrophiles in Vitro

Regulation of Human Mitochondrial Aldehyde Dehydrogenase (ALDH-2) Activity by Electrophiles in Vitro

Differential Effects of High Glucose and Methylglyoxal on Viability and Polyol Metabolism in Immortalized Adult Mouse Schwann Cells

Cellular Localization of Dieldrin and Structure–Activity Relationship of Dieldrin Analogues in Dopaminergic Cells

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