• 한국식품과학회지
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• 제34권5호
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• pp.905-910
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• 2002

한국인이 상용하는 식물성 유지로부터 n-3 지방산과 n-6 지방산 산화의 독성 산물인 4-hydroxy-2-hexenal(HHE)과 4-hydroxy-2-nonenal(HNE)를 높은 감도로 동시 정량 하기 위하여 GC/MS/SIM(m/z = 157)을 이용하여 정량 하고 노출량을 추정하였다. 한국인이 섭취하는 식물성 유지의 98%를 차지하는 4종류의 유지로부터 4-hydroxy-2-alkenals의 총 노출량은 $2.7\;{\mu}g/day$로 나타났고, 시장에서 수거한 튀김 기름의 경우에는 상온에서 보관한 유지류에 비해 높은 양의 HHE와 HNE가 검출되었다. 튀김 과정 중에 형성된 4-hydroxy-2-alkenals는 튀김 음식으로 이행될 가능성이 있으므로, 튀김 음식을 자주 섭취하는 집단은 4-hydroxy-2-alkenals에 대한 노출량이 더 높을 것으로 사료된다. n-3와 n-6 지방산의 생리 활성에 대한 보고로 인하여 이들 고도 불포화 지방산의 섭취가 증가하고 있으므로, 불포화 지방산을 다량 함유하고 있는 식품으로부터 n-3와 n-6 지방산의 특이적 산화 지표인 4-hydroxy-2-hexenal과 4-hydroxy-2-nonenal을 동시 정량 하여 식품 품질 및 안전성 평가를 하는 것은 바람직하다고 생각된다. 본 실험에서 보여 준, 상용 식물성 유지의 4-hydroxy-2-alkenals 함량에 관한 데이터는 식품을 통해 노출된 4-hydroxy-2-alkenals가 인체에 미치는 생리적 효과를 평가하기 위한 앞으로의 연구에 중요한 정보를 제공할 것이다.

• 한국어병학회지
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• 제16권1호
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• pp.39-49
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• 2003

Cytosolic oxidation by 4-hydroxy-2-nonenal (4HNE) and tert-butyl hydroperoxide (t-BHP) results in cell death of bovine aortic endothelial cells (BAEC). In this study, we have investigated the roles of antioxidants such as 2,3,6-tribromo-4,5-dihydroxy benzyl methyl ether (TDB) and phloroglucinol in preventing cell death. After treatment with oxidants for 6h, cells became compact and showed nuclear condensation, which were characteristics of early apoptosis. After l2h treatment, morphologic features including severe cytoplasm condensation, membrane blebbing, and apoptotic bodies were prominent and these findings were interpreted as characteristics of late-apoptosis. When the apoptotic cells were treated with antioxidants for 12h, both early and late apoptotic cells did show no significant change. After oxidant treated cells were incubated with antioxidant for 24h, the characteristics of early-apoptosis were eliminated but cells in lateapoptosis could not return to normal cells. These results suggest that TDB and phloroglucinol prevent the cells from dying through apoptosis induced by 4HNE and t-BHP in early stage.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.244.2-245
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• 2002

4-Hydroxy nonenal (HNE) is a lipid peroxidation product derived from oxidized $\omega$-6 polyunsaturated fatty acids, such as arachidonic acid. HNE is widely used as a marker of lipid peroxidation. To study the hypothesis that HNE may induce apoptosis and cell cycle arrest, we estimated cytotoxicity of HNE in BAE (bovine aortic endothelial) cells. Anti-proliferative effects were examined by morphological changes and MTT assay after exposure to different time (0-3 hr) and concentration (3-7 ${\mu}$M of HNE. (omitted)

• Nutrition Research and Practice
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• 제16권6호
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• pp.729-744
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• 2022

BACKGROUND/OBJECTIVES: 4-Hydroxy-2-nonenal (HNE) is a biomarker for oxidative stress to induce inflammation. Methionine is an essential sulfur-containing amino acid with antioxidative activity. On the other hand, the evidence on whether and how methionine can depress HNE-derived inflammation is lacking. In particular, the link between the regulation of the nuclear factor-κB (NF-κB) signaling pathway and methionine intake is unclear. This study examined the link between depression from HNE accumulation and the anti-inflammatory function of ⳑ-methionine in rats. MATERIALS/METHODS: Male Wistar rats (3-week-old, weighing 70-80 g) were administered different levels of ⳑ-methionine orally at 215.0, 268.8, 322.5, and 430.0 mg/kg body weight for two weeks. The control group was fed commercial pellets. The hepatic HNE contents and the protein expression and mRNA levels of the inflammatory mediators were measured. The interleukin-10 (IL-10) and glutathione S-transferase (GST) levels were also estimated. RESULTS: Compared to the control group, hepatic HNE levels were reduced significantly in all groups fed ⳑ-methionine, which were attributed to the stimulation of GST by ⳑ-methionine. With decreasing HNE levels, ⳑ-methionine inhibited the activation of NF-κB by up-regulating inhibitory κBα and depressing phosphoinositide 3 kinase/protein kinase B. The mRNA levels of the inflammatory mediators (cyclooxygenase-2, interleukin-1β, interleukin-6, inducible nitric oxide synthase, tumor necrotic factor alpha) were decreased significantly by ⳑ-methionine. In contrast, the protein expression of these inflammatory mediators was effectively down regulated by ⳑ-methionine. The anti-inflammatory action of ⳑ-methionine was also reflected by the up-regulation of IL-10. CONCLUSIONS: This study revealed a link between the inhibition of HNE accumulation and the depression of inflammation in growing rats, which was attributed to ⳑ-methionine availability. The anti-inflammatory mechanism exerted by ⳑ-methionine was to inhibit NF-κB activation and to up-regulate GST.

• Archives of Pharmacal Research
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• 제26권12호
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• pp.1047-1054
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• 2003

Molecular chaperones have a crucial role in the folding of nascent polypeptides in endoplasmic reticulum. Some of them are known to be sensitive to the modification by electrophilic metabolites of organic pro-toxicants. In order to identify chaperone proteins sensitive to alkyators, ER extract was subjected to alkylation by 4-acetamido-4 -maleimidyl-stilbene-2,2 -disulfonate (AMS), and subsequent SDS-PAGE analyses. Protein spots, with molecular mass of 160, 100, 57 and 36 kDa, were found to be sensitive to AMS alkylation, and one abundant chaperon protein was identified to be protein disulfide isomerase (PDI) in comparison with the purified PDI. To see the reactivity of PDI with cysteine alkylators, the reduced form ($PDI_{red}$) of PDI was incubated with various alkylators containing Michael acceptor structure for 30 min at $38^{\circ}C$ at pH 6.3, and the remaining activity was determined by the insulin reduction assay. Iodoacetamide or N-ethylmaleimide at 0.1 mM remarkably inactivated $PDI_{red}$ with N-ethylmaleimide being more potent than iodoacetamide. A partial inactivation of $PDI_{oxid}$ was expressed by iodoacetamide, but not N-ethylmaleimide (NEM) at pH 6.3. Of Michael acceptor compounds tested, 1,4-benzoquinone ($IC_{50}, 15 \mu$ M) was the most potent, followed by 4-hydroxy-2-nonenal and 1,4-naphthoquinone. In contrast, 1,2-naphthoquinone, devoid of a remarkable inactivation action, was effective to cause the oxidative conversion of $PDI_{red}$ to $PDI_{oxid}$. Thus, the action of Michael acceptor compounds differed greatly depending on their structure. Based on these, it is proposed that POI, one of chaperone proteins in ER, could be susceptible to endogenous or xenobiotic Michael acceptor compounds in vivo system.

• Biomolecules & Therapeutics
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• 제23권4호
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• pp.374-378
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• 2015

The purpose of the present study was to investigate the effects of resveratrol supplementation on oxidative damage and lipid peroxidation induced by strenuous exercise in rats. The rats were randomly divided into five groups: a sedentary control group, an exercise control group, and three treatment exercise groups administered increasing doses of resveratrol (25, 50, and 100 mg/kg body weight). Resveratrol was administered by oral gavage once daily for four weeks. At the end of the four-week period, the rats performed a strenuous exercise on the treadmill, and the levels of lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured. The results showed that resveratrol supplementation had protective effects against strenuous exercise-induced oxidative damage and lipid peroxidation by lowering the levels of LDH, CK, MDA, 4-HNE, and 8-OHdG in the serum or muscle of rats. These beneficial effects are probably owing to the inherent antioxidant activities of resveratrol.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.229.2-230
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• 2003

Among the aldehydes derived from lipid peroxidation, 4-hydroxynonenal (HNE) that can be produced from arachidonic acids. linoleic acids, or their hydroperoxides in relatively large amounts in response to oxidative insult. Therefore, HNE might be an important mediator of Oxidative stress-induced apoptosis. To study the hypothesis that HNE may induce apoptosis, we estimated cytotoxicity of HNE on YPEN-1 rat prostatic endothelial cells. (omitted)

• Toxicological Research
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• 제27권1호
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• pp.1-6
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• 2011

Lipid peroxidation is a free radical oxidation of polyunsaturated fatty acids such as linoleic acid or arachidonic acid. This process has been related with various pathologies and disease status mainly because of the oxidation products formed during the process. The oxidation products include reactive aldehydes such as malondialdehyde and 4-hydroxynonenal. These reactive aldehydes can form adducts with DNAs and proteins, leading to the alterations in their functions to cause various diseases. This review will provide a short summary on the implication of lipid peroxidation on cancer, atherosclerosis, and neurodegeneration as well as chemical and biochemical mechanisms by which these adducts affect the pathological conditions. In addition, select examples will be presented where antioxidants were used to counteract oxidative damage caused by lipid peroxidation. At the end, isoprostanes are discussed as a gold standard for the assessment of oxidative damages.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.24-25
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• 2001

Persistent cellular oxidative stress and enhanced lipid peroxidation (LPO) of PUFAs, leading to macromolecular damage and disruption of signaling pathways, are implicated in the development of human malignancies and other chronic degenerative diseases. LPO generates by oxidation of linoleic acid (LA) or arachidonic acid ($\omega$ -6 PUPAs) reactive aldehydes, such as trans-4-hydroxy-2-nonenal, which form etheno $\varepsilon$ -DNA adducts in a variety of human tissues and thus can contribute to diet-related cancers.(omitted)

• BMB Reports
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• 제36권1호
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• pp.95-109
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• 2003

Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance. The sources of the increased oxidative stress in patients with chronic inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD) derive from the increased burden of inhaled oxidants, and from the increased amounts of reactive oxygen species (ROS) generated by several inflammatory, immune and various structural cells of the airways. Increased levels of ROS produced in the airways is reflected by increased markers of oxidative stress in the airspaces, sputum, breath, lungs and blood in patients with lung diseases. ROS, either directly or via the formation of lipid peroxidation products such as 4-hydroxy-2-nonenal may play a role in enhancing the inflammation through the activation of stress kinases (JNK, MAPK, p38) and redox sensitive transcription factors such as NF-${\kappa}B$ and AP-1. Recent evidences have indicated that oxidative stress and pro-inflammatory mediators can alter nuclear histone acetylation/deacetylation allowing access for transcription factor DNA binding leading to enhanced pro-inflammatory gene expression in various lung cells. Understanding of the mechanisms of redox signaling, NF-${\kappa}B$/AP-1 regulation, the balance between histone acetylation and deacetylation and the release and expression of pro- and anti-inflammatory mediators may lead to the development of novel therapies based on the pharmacological manipulation of antioxidants in lung inflammation and injury. Antioxidants that have effective wide spectrum activity and good bioavailability, thiols or molecules which have dual antioxidant and anti-inflammatory activity, may be potential therapeutic agents which not only protect against the direct injurious effects of oxidants, but may fundamentally alter the underlying inflammatory processes which play an important role in the pathogenesis of chronic inflammatory lung diseases.