Accumulation of protein-bound 4-hydroxy-2-hexenal in spinal cords from patients with sporadic amyotrophic lateral sclerosis

Shibata, Noriyuki; Yamada, Satoshi; Uchida, Koji; Hirano, Atsushi; Sakoda, Saburo; Fujimura, Harutoshi; Sasaki, Shoichi; Iwata, Makoto; Toi, Sono; Kawaguchi, Motoko; Yamamoto, Tomoko; Kobayashi, Makio

doi:10.1016/j.brainres.2004.05.110

Cited by 38 publications

(30 citation statements)

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“…Feeding animals with highly oxidized n -6 fat was reported to increase the expression of markers of intestine antioxidant defense ( 36,37 ). Here we show a signifi cant increase in GPx2 mRNA after diseases ( 14,16 ). Here we found that when 4-HHE was orally administrated to mice, it reacted with functional proteins to form adducts in the duodenum and, to a lower extent, in the jejunum.…”

Section: Discussionsupporting

confidence: 52%

“…These lipid aldehydes are prone to react with thiol and amine moieties and produce Schiff base and/or Michael adducts with biomole cules, such as proteins, DNA, and phospholipids ( 12,13 ). Numerous studies reported the genotoxicity and cytotoxicity of these 4-hydroxy-2-alkenals on tissues and cells in pathophysiological contexts (14)(15)(16), but nothing is known to date about the possible contribution of 4-hydroxy-2-alkenals present in food products, their fate after ingestion, and their metabolic effects.…”

Section: Caco-2/tc7 Cell Culture and Treatmentmentioning

confidence: 99%

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Dietary oxidized n-3 PUFA induce oxidative stress and inflammation: role of intestinal absorption of 4-HHE and reactivity in intestinal cells

Awada

Soulage

Meynier

et al. 2012

Journal of Lipid Research

174

154

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Section: Discussionsupporting

confidence: 52%

Section: Caco-2/tc7 Cell Culture and Treatmentmentioning

confidence: 99%

Dietary oxidized n-3 PUFA induce oxidative stress and inflammation: role of intestinal absorption of 4-HHE and reactivity in intestinal cells

Awada

Soulage

Meynier

et al. 2012

Journal of Lipid Research

174

154

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“…4-HHE and CRA are the α,β-unsaturated aldehydes that are end products of oxidation of n-3 fatty acids [6,29]. These highly reactive aldehydes readily attack and modify the protein amino acid residues to protein-bound 4-HHE/CRA, such as 4-HHE-histidine adduct and CRAlysine adduct [39,41]. However, the production and localization of these PUFA oxidation markers are unclear in the development of APAP-induced liver injury.…”

mentioning

confidence: 99%

“…Recently, polyunsaturated fatty acid (PUFA) oxidation markers, such as N ε -propanoyl-modified lysine (PRL), N ε -hexanoyl-modified lysine (HEL) 4-hydroxyhexenal-modified histidine (4-HHE-histidine) and crotonaldehyde-modified lysine (CRA-lysine), have been given more attention as factors related to the processes of diverse pathological situations [9,15,19,21,23,33,[38][39][40]44]. PUFA is easily peroxidized by free radicals and enzymes, and peroxidation of PUFA results in compromised integrity of cellular membranes and leads to lipid hydroperoxide as a major reaction product, and lipid hydroperoxide is decomposed into aldehyde [20].…”

mentioning

confidence: 99%

Immunohistochemical Detection of Polyunsaturated Fatty Acid Oxidation Markers in Acetaminophen-Induced Liver Injury in Rats

Sun

Sugiyama

Hisaka

et al. 2012

The Journal of Veterinary Medical Science

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ABSTRACT. To clarfity whether polyunsaturated fatty acid (PUFA) oxidation is involved in the mechanism of acetaminophen (APAP)-induced apoptotic cell death, the production and localization of PUFA oxidation markers N  -propanoyl-modified lysine, N  -hexanoylmodified lysine, 4-hydroxyhexenal-modified histidine and crotonaldehyde-modified lysine were evaluated in the development of APAPinduced liver injury. The immunoexpression of these markers in the liver was examined up to 24 hr post-APAP intraperitoneal injection in rats (1 g/kg body weight). The histopathological changes in the liver appeared 3 hr after APAP injection and became exacerbated with time. Proapoptotic protein Bax immunoreactivity was first detected in the degenerative hepatocytes 3 hr after the injection and areas positively immunostained for Bax reached a peak level at 6 hr, and then decreased at 12 and 24 hr. There was a significant increase in the TUNEL-positive rate at 12 and 24 hr. Immunohistological expression of all these oxidation markers was first detected in the degenerative hepatocytes 3 hr after the injection, and earlier than the occurrence of hepatocyte apoptosis. Immunohistochemical expression of these markers were observed in almost all degenerative hepatocytes 3-24 hr after APAP injection. Areas positively immunostained for these markers reached a peak level at 6 hr, and then decreased at 12 and 24 hr. The results thus suggest that the generation of PUFA oxidation markers may be the signature of early events preceding the induction of liver cell apoptosis and thus useful for early detection of oxidative stress-related liver cell injury.

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“…106 Elevados níveis de adutos de HHE-histidina também foram encontrados na medula espinhal de pacientes com ALS. 107 O HHE é um aldeído formado a partir da oxidação não enzimática do DHA e a detecção deste aduto indica que este ácido graxo é um alvo importante de oxidação na doença. Dado que o DHA é mais abundante que o AA no cérebro, também os neuroprostanos e neurofuranos podem se revelar biomarcadores atrativos.…”

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Metabolismo, oxidação e implicações biológicas do ácido docosahexaenoico em doenças neurodegenerativas

Appolinário¹,

Derogis²,

Yamaguti³

et al. 2011

Quím. Nova

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Recebido em 16/8/10; aceito em 20/4/11; publicado na web em 8/7/11 METABOLISM, OXIDATION AND BIOLOGICAL IMPLICATIONS OF DOCOSAHEXAENOIC ACID IN NEURODEGENERATIVE DISEASES. Docosahexaenoic acid (C22:6, n-3, DHA) is a polyunsaturated fatty acid (PUFA) present in large concentrations in the brain and, due to the presence of six double bonds in its structure, is highly susceptible to oxidation by enzymes and reactive oxygen/nitrogen species. The peroxidation of PUFAs has been implicated in an increasing number of human disorders, including neurodegenerative diseases. Hence, a better understanding of the metabolism pathways of DHA should provide new insights about its role in neurodegenerative diseases. Here we review the main aspects related to DHA metabolism, as well as, the recent findings showing its association with neurodegenerative diseases.Keywords: docosahexaenoic acid; metabolism; neurodegenerative diseases. INTRODUÇÃOOs lipídios constituem um grupo heterogêneo de compostos que têm papel crucial na célula, cuja característica comum é a solubilidade em solventes orgânicos e insolubilidade na água. As funções biológicas dos mesmos são tão diversas quanto a sua química. Sua importância pode ser notada pelo número crescente de estudos apontando o envolvimento de seus produtos de oxidação e de disfunções no metabolismo de lipídios em doenças crônico-degenerativas. 1-4Os ácidos graxos são ácidos carboxílicos com cadeias de hidrocarbonetos contendo de 4 a 36 carbonos, sendo encontrados principalmente esterificados a triglicerídios, colesterol e fosfolipídios constituintes das membranas celulares. Eles podem ser classificados em saturados (contendo apenas ligações simples), monoinsaturados (uma ligação dupla) ou poli-insaturados (duas ou mais ligações duplas). Os ácidos graxos poli-insaturados podem ser representados usando-se a abreviação estrutural que os identifica única e exclusivamente através do número de carbonos e de duplas ligações. Também podem ser denominados a partir da posição das ligações duplas, em relação ao grupamento metila terminal, utilizando-se para tanto a denominação ω ou n, 5 sendo a denominação n a recomendada pela IUPAC. 6Estudos mostram que os ácidos graxos poli-insaturados n-3 (ômega-3) e n-6 (ômega-6) têm efeitos distintos nas células, sendo o primeiro associado a efeitos benéficos e o segundo, a efeitos deletérios. 7,8 Os ácidos linoleico (18:2n-6) e linolênico (18:3n-3) são os precursores dos ácidos graxos n-6 e n-3, respectivamente. São considerados essenciais por não serem sintetizados de novo pelos tecidos de vertebrados, sendo necessária a ingestão destes pela dieta. 9O ácido docosahexaenoico (4,7,10,13,16,19-22:6, DHA) é um ácido graxo ômega-3 de 22 carbonos e 6 insaturações. Está enriquecido nas membranas neurais do córtex cerebral e na retina, 10,11 onde 25-35% se encontram esterificados em aminofosfolipídios como a fosfatidilserina, fosfatidiletanolamina e em plasmalogênios.12,13 O DHA constitui > 17% do peso total de ácidos graxos no cérebro de ratos adultos e > 33% do total ...

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Accumulation of protein-bound 4-hydroxy-2-hexenal in spinal cords from patients with sporadic amyotrophic lateral sclerosis

Cited by 38 publications

References 33 publications

Dietary oxidized n-3 PUFA induce oxidative stress and inflammation: role of intestinal absorption of 4-HHE and reactivity in intestinal cells

Dietary oxidized n-3 PUFA induce oxidative stress and inflammation: role of intestinal absorption of 4-HHE and reactivity in intestinal cells

Immunohistochemical Detection of Polyunsaturated Fatty Acid Oxidation Markers in Acetaminophen-Induced Liver Injury in Rats

Metabolismo, oxidação e implicações biológicas do ácido docosahexaenoico em doenças neurodegenerativas

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