• BMB Reports
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• 제37권3호
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• pp.325-329
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• 2004

Oxidation of catecholamines may contribute to the pathogenesis of Parkinson's disease (PD). The effect of the oxidized products of catecholamines on the modification of Cu,Zn-superoxide dismutase (SOD) was investigated. When Cu,Zn-SOD was incubated with the oxidized 3,4-dihydroxyphenylalanine (DOPA) or dopamine, the protein was induced to be aggregated. The deoxyribose assay showed that hydroxyl radicals were generated during the oxidation of catecholamines in the presence of copper ion. Radical scavengers, azide, N-acetylcysteine, and catalase inhibited the oxidized catecholamine-mediated Cu,Zn-SOD aggregation. Therefore, the results indicate that free radicals may play a role in the aggregation of Cu,Zn-SOD. When Cu,Zn-SOD that had been exposed to catecholamines was subsequently analyzed by an amino acid analysis, the glycine and histidine residues were particularly sensitive. These results suggest that the modification of Cu,Zn-SOD by oxidized catecholamines might induce the perturbation of cellular antioxidant systems and led to a deleterious cell condition.

• Biomolecules & Therapeutics
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• 제11권2호
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• pp.112-118
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• 2003

1-Methylated $\beta$-carbolines (harmaline and harmalol) and antioxidants (N-acetylcysteine and ascorbate) reduced the loss of cell viability in differentiated PC 12 cells treated with 5 mM glutamate. $\beta$-Carbolines prevented the glutamate-induced decrease in mitochondrial membrane potential, cytochrome c release and caspase-3 activation in PC 12 cells. $\beta$-Carbolines reduced the formation of reactive oxygen species and depletion of glutathione due to glutamate in PC12 cells. $\beta$-Carbolines revealed a scavenging action on hydrogen peroxide and reduced the iron and EDTA-mediated degradation of 2-deoxy-D-ribose. The results suggest that I-methylated $\beta$-carbolines attenuate the cytotoxic effect of glutamate on PC12 cells by reducing the alteration of mitochondrial membrane permeability that seems to be mediated by oxidative stress.

• 약학회지
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• 제43권3호
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• pp.385-390
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• 1999

Camptothecin (CPT) has been known to induce apoptosis in various cancer cell lines. To examine the intracellular apoptotic death signal initiated by CPT, we investigated the possible connection between caspase-3 activation and GSH depletion during CPT-induced apoptosis in HL-60 cells. Treatment of cells with $1{\;}{\mu}M$ CPT induced PARP cleavage accompanied by DNA fragmentation. z-VAD-fmk, a caspase-3 inhibitor, blocked the CPT-induced DNA fragmentation. Pretreatment of cells with N-acetylcysteine, a precursor of GSH biosynthesis, failed to inhibit CPT-induced PARP celavage and DNA gragmenatation. No significant changes in GSH depletion is not essential for caspase activation during CPT-induced apoptosis. We also investigated whether CPT-induced apoptosis is associated with changes of the levels of Bax and Bcl-2, two proteins involved in the control of apoptosis. Bcl-2 levels exhibited a late decrease compared with the kinetics of DNA fragmentation, whereas Bax levels increased more rapidly after CPT treatment. These results suggest that Bax plays more important role than Bcl-2 in inducing DNA fragmentation and may function upsteam of proteolytic activation of caspase-3 pathway in CPT-induced apoptosis.

• 대한수의학회지
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• 제57권1호
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• pp.55-57
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• 2017

A 5-year-old, 2.7 kg, spayed female Scottish Fold cat presented with hematemesis after administration of oral zaltoprofen, a non-steroidal anti-inflammatory drug, by the owner. Diagnostic imaging and blood analyses indicated development of acute kidney injury (AKI) resulting from zaltoprofen ingestion. To correct dehydration and anemic conditions, the cat received intravenous fluid therapy with whole blood transfusion and peroral N-acetylcysteine. Clinical signs resolved, but persistent azotemia was unresolved indicating that AKI could progress to chronic kidney disease. This case suggests that although zaltoprofen may have low adverse effects on humans, administration of zaltoprofen in cats can have serious adverse effects.

• Tuberculosis and Respiratory Diseases
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• 제74권1호
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• pp.1-6
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• 2013

The concept on idiopathic pulmonary fibrosis (IPF) pathogenesis has progressed from chronic inflammation to aberrant wounding healing and even more to the current paradigms of a multifactorial and heterogeneous disease process. Despite the growth of clinical trials for IPF, most of the results, including N-acetylcysteine combination, warfarin, and bosentan, were disappointing. On the other hand, there have been a number of important developments; the foremost is the licensing of pirfenidone in Europe and Asia. In this article, we briefly review the recent knowledge of pathogenesis of IPF. We also summarize the recent clinical trials regarding the management of IPF.

• Archives of Pharmacal Research
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• 제27권8호
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• pp.845-849
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• 2004

Many studies have focused on the anticarcinogenic, antimutagenic or chemopreventive activi-ties of capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) which is a major pungent ingredient in red pepper. We have previously shown that capsaicin selectively induces apoptosis in H-ras-transformed MCF10A human breast epithelial cells but not in their normal cell counter-parts (Int. J. Cancer, 103, 475-482,2003). In this study, we investigated the possible roles of reactive oxygen species (ROS) and Rac1 in capsaicin-induced apoptosis of H-ras MCF10A cells. Selective induction of ROS generation by capsaicin treatment was observed only in H-ras MCF10A cells. Pretreatment of H-ras MCF10A cells with an antioxidant N-acetylcysteine(NAC) significantly reversed capsaicin-induced growth inhibition, suggesting that ROS may mediate the apoptosis of H-ras-transformed cells induced by capsaicin. Rac1 was prominently activated by H-ras in MCF10A cells. Based on the studies using a wild type Rac1 and a domi-nant negative Rac1 constructs, we propose that Rac1 activity is critical for inhibitory effect of capsaicin on growth of H-ras-transformed MCF10A cells possibly through ROS generation.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5631-5635
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• 2013

Cochlea hair cell death is regarded to be responsible for the radiation-induced sensorineural hearing loss (SNHL), which is one of the principal complications of radiotherapy (RT) for head and neck cancers. In this mini-review, we focus on the current progresses trying to unravel mechanisms of radiation-induced hair cell death and find out possible protection. P53, reactive oxygen species (ROS) and c-Jun N-terminal kinase (JNK) pathways have been proposed as pivotal in the processes leading to radiation hair cell death. Potential protectants, such as amifostine, N-acetylcysteine (NAC) and epicatechin (EC), are claimed to be effective at reducing radiation-inducedhair cell death. The RT dosage, selection and application of concurrent chemotherapy should be pre-examined in order to minimize the damage to cochlea hair cells.

• Clinical and Experimental Reproductive Medicine
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• 제48권4호
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• pp.316-321
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• 2021

Objective: Amino acids can protect sperm structure in cryopreservation due to their antioxidant properties. Therefore, the present study aimed to investigate the protective effect of L-carnitine (LC) and N-acetyl cysteine (NAC) on motility parameters, plasma membrane integrity (PMI), mitochondrial membrane potential (MMP), DNA damage, and human sperm intracellular reactive oxygen species (ROS) during vitrification. Methods: Twenty normal human sperm samples were examined. Each sample was divided into six equal groups: LC (1 and 10 mM), NAC (5 and 10 mM), and cryopreserved and fresh control groups. Results: The groups treated with LC and NAC showed favorable findings in terms of motility parameters, DNA damage, and MMP. Significantly higher levels of intracellular ROS were observed in all cryopreserved groups than in the fresh group (p≤0.05). The presence of LC and NAC at both concentrations caused an increase in PMI, MMP, and progressive motility parameters, as well as a significant reduction in intracellular ROS compared to the control group (p≤0.05). The concentrations of the amino acids did not show any significant effect. Conclusion: LC and NAC are promising as potential additives in sperm cryopreservation.

• Tuberculosis and Respiratory Diseases
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• 제58권3호
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• pp.267-276
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• 2005

연구배경 : 전환성장인자-${\beta}1$(transforming growth factor-${\beta}1$: $TGF-{\beta}1$)은 폐 섬유화를 매개하는 주된 인자이지만 $TGF-{\beta}1$에 의한 폐 섬유화의 발생과 진행기전의 이해는 아직 불완전하다. $TGF-{\beta}1$은 다양한 세포에서 활성산소족(reactive oxygen species: ROS)을 통하여 세포내 신호를 전달하고 ${\alpha}$-smooth muscle actin (${\alpha}$-SMA)의 신생합성을 통하여 상피세포와 폐 섬유아세포를 근 섬유아세포 표현형으로의 변화를 유도하는 주된 인자이다. ROS는 또 다양한 세포에서 세포외기질 (extracellular matrix: ECM) 축적을 유발하는 것이 알려져 있음으로 본 연구에서는 폐 섬유아세포인 MRC-5 세포에서 $TGF-{\beta}1$이 ROS를 매개하여 fibronectin 분비와 ${\alpha}-SMA$ 표현의 증가에 관여하는지를 검색하였다. 방 법 : 성장이 동일화된 MRC-5 세포를 $TGF-{\beta}1$ (0.2-10ng/ml)으로 96 시간까지 자극하였고, 필요에 따라 항산화제인 N-acetylcysteine (NAC)이나 NADPH oxidase 억제제인 diphenyleniodonium (DPI)을 $TGF-{\beta}1$ 투여 1 시간 전부터 전처리하였다. Dichlorofluorescein (DCF)에 민감한 세포내 ROS는 FACS로, 분비된 fibronectin과 세포의 ${\alpha}-SMA$ 표현은 Western blot 분석으로 측정하였다. 결 과 : $TGF-{\beta}1$은 용량의존적으로 fibronectin 분비와 ${\alpha}-SMA$ 표현을 상향조절하였다. NAC와 DPI는 $TGF-{\beta}1$에 의한 fibronectin 분비 증가와 ${\alpha}-SMA$ 상향조절을 유의하게 억제하였다. $TGF-{\beta}1$에 의한 세포내 ROS의 증가도 NAC나 DPI에 의하여 유의하게 억제되었다. 결 론 : 본 연구의 결과는 폐 섬유아세포에서 NADPH oxidase 에 의하여 생산된 ROS가 $TGF-{\beta}1$에 의한 fibronectin 분비와 ${\alpha}-SMA$ 표현을 상향조절함으로써 폐 섬유화의 발생과 진행에 관여할 수 있음을 증명하였다.

• 생명과학회지
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• 제22권4호
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• pp.538-544
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• 2012

에탄올은 사람에 대한 발암물질로 잘 알려져 있다. 또한 여러 조직이나 세포에서의 에탄올에 의한 세포증식억제효과도 잘 알려져 있다. 본 연구에서는 여러 암세포에서 에탄올에 의한 세포증식억제 효과를 조사하였는데 특히 발암원성 $ras$로 형질전환되거나 미세주입된 세포에서의 영향을 조사하였다. 에탄올은 여러 정상세포들의 증식을 억제하였다. 반면에 여러 암세포나 발암원성 Ras에 의한 세포증식은 억제하지 못 하였다. 또한 발암원성 단백질의 세포내 미세주사에 의한 DNA합성 유도도 에탄올에 의해 억제 되지 않았다. 이러한 에탄올의 세포증식억제 효과는 $N$-acetylcysteine이나 4-methylpyrazole과 같은 항산화제에 의해 제거되었다. 이러한 실험 결과는 에탄올에 의한 세포증식억제 효과는 Ras단백질의 upstream에 있거나 또는 Ras와 독립적으로 작용하며, 활성산소 형성과 밀접한 관계가 있다는 것을 알려준다.