• Advances in Traditional Medicine
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• 제4권3호
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• pp.211-214
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• 2004

The inhibitory effect of dl-puerol A as but-2-enolide isolated from Sophora japonica was investigated on copper ion-induced protein oxidative modification in vitro. It inhibited copper-induced protein oxidative modification. However, its inhibitory effect was a little weaker than that of $dl-{\alpha}-tocopherol$ as an antioxidant. The results demonstrated that dl-puerol A, one of but-2-enolides, might be of use in the oxidative stress.

• BMB Reports
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• 제36권5호
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• pp.488-492
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• 2003

Neurofilament-L (NF-L) is a major element of neuronal cytoskeletons and known to be important for neuronal survival in vivo. Since oxidative stress might play a critical role in the pathogenesis of neurodegenerative diseases, we investigated the role of copper and peroxide in the modification of NF-L. When disassembled NF-L was incubated with copper ion and hydrogen peroxide, then the aggregation of protein was proportional to copper and hydrogen peroxide concentrations. Dityrosine crosslink formation was obtained in copper-mediated NF-L aggregates. The copper-mediated modification of NF-L was significantly inhibited by thiol antioxidants, N-acetylcysteine, glutathione, and thiourea. A thioflavin-T binding assay was performed to determine whether the copper/$H_2O_2$ system-induced in vitro aggregation of NF-L displays amyloid-like characteristics. The aggregate of NF-L displayed thioflavin T reactivity, which was reminiscent of amyloid. This study suggests that copper-mediated NF-L modification might be closely related to oxidative reactions which may play a critical role in neurodegenerative diseases.

• BMB Reports
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• 제45권2호
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• pp.114-119
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• 2012

Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline) is a compound derived from dopamine metabolism and is capable of causing dopaminergic neurodegeneration. Oxidative modification of neurofilament proteins has been implicated in the pathogenesis of neurodegenerative disorders. In this study, oxidative modification of neurofilament-L (NF-L) by salsolinol and the inhibitory effects of histidyl dipeptides on NF-L modification were investigated. When NF-L was incubated with 0.5 mM salsolinol, the aggregation of protein was increased in a time-dependent manner. We also found that the generation of hydroxyl radicals (${\bullet}OH$) was linear with respect to the concentrations of salsolinol as a function of incubation time. NF-L exposure to salsolinol produced losses of glutamate, lysine and proline residues. These results suggest that the aggregation of NF-L by salsolinol may be due to oxidative damage resulting from free radicals. Carnosine, histidyl dipeptide, is involved in many cellular defense processes, including free radical detoxification. Carnosine, and anserine were shown to significantly prevent salsolinol-mediated NF-L aggregation. Both compounds also inhibited the generation of ${\bullet}OH$ induced by salsolinol. The results indicated that carnosine and related compounds may prevent salsolinol-mediated NF-L modification via free radical scavenging.

• Toxicological Research
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• 제33권1호
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• pp.1-5
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• 2017

Nuclear factor E2-related factor 2 (Nrf2), a transcription factor, controls the expression of genes encoding cytoprotective proteins, including antioxidant enzymes that combat oxidative and electrophilic stress to maintain redox homeostasis. However, recent studies demonstrated that, in cancer, aberrant activation of Nrf2 by epigenetic alterations promotes high expression of cytoprotective proteins, which can decrease the efficacy of anticancer drugs used for chemotherapy. In this review, we summarize recent findings regarding the relationship between oxidative stress, Nrf2, epigenetic modification, and anticancer drug resistance, which should aid in development of new strategies to improve chemotherapeutic efficacy.

• Bulletin of the Korean Chemical Society
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• 제34권11호
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• pp.3295-3300
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• 2013

Acrolein (ACR) is a well-known carbonyl toxin produced by lipid peroxidation of polyunsaturated fatty acids, which is involved in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). In Alzheimer's brain, ACR was found to be elevated in hippocampus and temporal cortex where oxidative stress is high. In this study, we evaluated oxidative modification of cytochrome c occurring after incubation with ACR. When cytochrome c was incubated with ACR, protein aggregation increased in a dose-dependent manner. The formation of carbonyl compounds and the release of iron were obtained in ACR-treated cytochrome c. Reactive oxygen species scavengers and iron specific chelator inhibited the ACR-mediated cytochrome c modification and carbonyl compound formation. Our data demonstrate that oxidative damage of cytochrome c by ACR might induce disruption of cyotochrome c structure and iron mishandling as a contributing factor to the pathology of AD.

• BMB Reports
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• 제44권3호
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• pp.165-169
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• 2011

Excess free iron generates oxidative stress that may contribute to the pathogenesis of various causes of neurodegenerative diseases. In this study, we assessed the modification of ferritin induced by $H_2O_2$. When ferritin was incubated with $H_2O_2$, the degradation of ferritin L-chain increased with the $H_2O_2$ concentration whereas ferritin H-chain was remained. Free radical scavengers, azide, thiourea, and N-acetyl-$_L$-cysteine suppressed the $H_2O_2$-mediated ferritin modification. The iron specific chelator, deferoxamine, effectively prevented $H_2O_2$-mediated ferritin degradation in modified ferritin. The release of iron ions from ferritin was increased in $H_2O_2$ concentration-dependent manner. The present results suggest that free radicals may play a role in the modification and iron releasing of ferritin by $H_2O_2$. It is assumed that oxidative damage of ferritin by $H_2O_2$ may induce the increase of iron content in cells and subsequently lead to the deleterious condition.

• 한국응용과학기술학회지
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• 제35권1호
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• pp.194-204
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• 2018

본 연구는 신경퇴행성질환과 밀접한 관련이 있는 neurofilament-L(NF-L)의 산화적 손상에 엄나무 발효물이 미치는 영향을 알아보고자 하였다. 용액 상에서 peroxyl radical을 생성하는 AAPH를 처리하여 NFL의 산화적 변형을 유도하고 엄나무 추출물(KP), 노루궁뎅이버섯 균사체 추출물(HE), 엄나무 발효물(KP-HE)을 각각 처리하여 어떤 영향을 미치는 지를 알아보고자 하였다. KP와 HE는 peroxyl radical에 의한 NF-L의 산화적 손상을 막지 못했으나 KP-HE는 NF-L의 변형을 효과적으로 억제하였다. KP-HE는 peroxyl radical에 의한 NF-L 변형에서 나타나는 dityrosine 형성을 효과적으로 억제하였고 peroxyl radical 소거활성도 증가시켰다. 파킨슨병 환자에서 발견되는 신경독성물질인 tetrahydropapaveroline(THP)에 의한 NFL의 변형에 KP, HE, KP-HE가 미치는 영향을 관찰하였다. 그 결과 KP-HE는 KP와 HE에 비해서 THP에 의한 NF-L의 변형을 효과적으로 억제하는 것으로 관찰되었다. 또한 KP-HE는 THP에 의한 NF-L 변형에서 나타나는 dityrosine 형성도 효과적으로 억제하였고 THP에 의해 유도되는 활성산소 생성도 현저히 감소시켰다. 이와 같은 결과들은 KP-HE가 활성산소와 신경독성물질에 의한 산화적 스트레스로부터 세포를 보호해 줄 수 있을 것으로 사료되었다. 그러므로 엄나무 발효물은 신경퇴행성질환을 예방할 수 있는 식품소재로 이용될 수 있을 것으로 사료된다.

• BMB Reports
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• 제46권2호
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• pp.119-123
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• 2013

Methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (salsolinol), an endogenous neurotoxin, is known to perform a role in the pathogenesis of Parkinson's disease (PD). In this study, we evaluated oxidative modification of cytochrome c occurring after incubation with salsolinol. When cytochrome c was incubated with salsolinol, protein aggregation increased in a dose-dependent manner. The formation of carbonyl compounds and the release of iron were obtained in salsolinol-treated cytochrome c. Salsolinol also led to the release of iron from cytochrome c. Reactive oxygen species (ROS) scavengers and iron specific chelator inhibited the salsolinol-mediated cytochrome c modification and carbonyl compound formation. It is suggested that oxidative damage of cytochrome c by salsolinol might induce the increase of iron content in cells, subsequently leading to the deleterious condition which was observed. This mechanism may, in part, provide an explanation for the deterioration of organs under neurodegenerative disorders such as PD.

• Bulletin of the Korean Chemical Society
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• 제34권2호
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• pp.406-410
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• 2013

Tetrahyropapaveroline (THP) is compound derived from dopamine metabolism and is capable of causing dopaminergic neurodegenerative disorder, such as Parkinson's disease (PD). The aim of this study was to evaluate the potential of THP to cause oxidative damage on the structure of cytochrome c (cyt c). Our data showed that THP led to protein aggregation and the formation of carbonyl compound in protein aggregates. THP also induced the release of iron from cyt c. Reactive oxygen species (ROS) scavengers and iron specific chelator inhibited the THP-mediated cyt c modification and carbonyl compound formation. The results of this study show that ROS may play a critical role in THP-induced cyt c modification and iron releasing of cyt c. When cyt c that has been exposed to THP was subsequently analyzed by amino acid analysis, lysine, histidine and methionine residues were particularly sensitive. It is suggested that oxidative damage of cyt c by THP might induce the increase of iron content in cells and subsequently led to the deleterious condition. This mechanism is associated with the deterioration of organs under neurodegenerative disorder such as PD.

• 약학회지
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• 제45권5호
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• pp.529-536
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• 2001

The root of Astragalus membranaceus Bunge (Leguminosae), which has been used for the treatment of hypertension, chronic hepatitis, duodenal ulcers, chronic nephritis and promotion of immunity in folk remedies. Several lines of evidence indicate that oxidative modification of low-density lipoprotein (Ox-LDL) may play an important role in atherogenesis. Hence, the role of antioxidants in the prevention of LDL oxidation needs to be determined. To investigate the antioxidant activity. we determined the MeOH ex. and fractions of Astragali Radix on the inhibition of LDL oxidation. The CH$_2$C1$_2$ and EtOAc orations inhibited the oxidative modification of LDL by a decrease in the lipid peroxide content and the electrophoretic mobility of LDL. Calycosin-7-0-$\beta$-D -glucoside which was isolated from EtOAc fraction inhibits the oxidative modification of LDL.