• Molecules and Cells
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• 제40권4호
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• pp.280-290
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• 2017

Several lines of evidence suggest that endoplasmic reticulum (ER) stress plays a critical role in the pathogenesis of many neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Protein tyrosine phosphatase 1B (PTP1B) is known to regulate the ER stress signaling pathway, but its role in neuronal systems in terms of ER stress remains largely unknown. Here, we showed that rotenone-induced toxicity in human neuroblastoma cell lines and mouse primary cortical neurons was ameliorated by PTP1B inhibition. Moreover, the increase in the level of ER stress markers ($eIF2{\alpha}$ phosphorylation and PERK phosphorylation) induced by rotenone treatment was obviously suppressed by concomitant PTP1B inhibition. However, the rotenone-induced production of reactive oxygen species (ROS) was not affected by PTP1B inhibition, suggesting that the neuroprotective effect of the PTP1B inhibitor is not associated with ROS production. Moreover, we found that MG132-induced toxicity involving proteasome inhibition was also ameliorated by PTP1B inhibition in a human neuroblastoma cell line and mouse primary cortical neurons. Consistently, downregulation of the PTP1B homologue gene in Drosophila mitigated rotenone- and MG132-induced toxicity. Taken together, these findings indicate that PTP1B inhibition may represent a novel therapeutic approach for ER stress-mediated neurodegenerative diseases.

• 한국응용곤충학회지
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• 제62권4호
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• pp.267-275
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• 2023

제충국(Tanacetum cineariaiaefolium), 데리스(Derris elliptica), 고삼(Sophora flavescens) 추출물은 다양한 해충을 방제하는데 사용되고 있다. 하지만, 국내에서 판매되고 있는 식물추춞물 자재는 유효성분의 표기가 없고, 살충농도와 살충시간에 대한 자료가 전무한 상황이다. 본 연구에서는 상용화된 주요 식물추출물의 살충유효성분의 농도를 결정하고 복숭아혹진딧물에 대해 살충농도와 살충시간을 측정하였다. 식물추출물의 살충활성성분인 pyrethrins, rotenone, matrine과 oxymatrine의 농도는 액체 크로마토그래피에서 표준물질을 활용하여 질량분석을 통해 측정하였다. 식물추출물을 농도별로 희석하여 복숭아혹진딧물에 살포하여 살충력을 측정하였다. 표준화합물과 비교한 후 질량분석 및 결정했습니다. Myzus persicae에 대한 lethal concentation과 lethal time을 조사했다. 살포 후 48시간 후 치사 농도(LC50)는 pyrethrins (20.4 ppm), roteone (34.1 ppm), matrine (29.6 ppm)였고, 100 ppm 살포한 LT50은 pyrethrins (13.4시간), rotenone (15.1시간), matrine (14.4시간)로 측정되었다. Kaplan-Meier 생존분석 결과, 100 ppm에서 세 가지 식물 추출물의 LT50은 대조구인 화학 살충제인 Sulfoxaflor를 살포 처리구보다 유의하게 빨랐습니다. 본 결과는 복숭아혹진딧물 방제를 위해 식물추출물의 제형화에 단일 또는 혼합 제제를 개발하는데 기준 살충농도와 살충시간을 제고하는데 의미가 있다.

• 한국수정란이식학회지
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• 제25권1호
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• pp.35-42
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• 2010

Many studies propose that dysfunction of mitochondrial proton-translocating NADH-ubiquinone oxidoreductase (complex I) is associated with neurodegenerative disorders, such as Parkinson's disease and Huntington's disease. Mammalian mitochondrial proton-translocating NADH-quinone oxidoreductase (complex I) consists of at least 46 different subunits. In contrast, the NDI1 gene of Saccharomyces cerevisiae is a single subunit rotenone-insensitive NADH-quinone oxidoreductase that is located on the matrix side of the inner mitochondrial membrane. With a recombinant adeno-associated virus vector carrying the NDI1 gene (rAAV-NDI1) as the gene delivery method, we were able to attain high transduction efficiencies even in the human epithelial cervical cancer cells that are difficult to transfect by lipofection or calcium phosphate precipitation methods. Using a rAAV-NDI1, we demonstrated that the Ndi1 enzyme is successfully expressed in HeLa cells. The expressed Ndi1 enzyme was recognized to be localized in mitochondria by confocal immunofluorescence microscopic analyses and immunoblotting. Using digitonin-permeabilized cells, it was shown that the NADH oxidase activity of the NDI1-transduced HeLa cells were not affected by rotenone which is inhibitor of complex I, but was inhibited by flavone and antimycin A. The NDI1-transduced cells were able to grow in media containing rotenone. In contrast, control cells that did not receive the NDI1 gene failed to survive. In particular, in the NDI1-transduced cells, the yeast enzyme becomes integrated into the human respiratory chain. It is concluded that the NDI1 gene provides a potentially useful tool for gene therapy of mitochondrial diseases caused by complex I deficiency.

• 한방안이비인후피부과학회지
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• 제22권3호
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• pp.20-35
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• 2009

Objective : The present study designed this study to investigate anti-oxidative effects of EF on HaCaT keratinocyte. Method : The present study measured the amount of polyphenoics and flavonoids, and also measured the levels of catalase, Ascorbate peroxidase (APX), SOD like activities and DPPH free radical scavenging activity. Then the effects of SB on viability and prolferation rates, and protective effects against oxidative stress induced by chemicals such as hydrogen peroxide and rotenone were also investigated. Results and conclusion : EF showed protective effect against cell death of HaCaT keratinocyte induced by rotenone and SNP significantly. In conclusion, these results suggest that EF may have anti-oxidantic action in human skin and also suggest that EF can be used as anti-aging agent.

• Bulletin of the Korean Chemical Society
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• 제33권4호
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• pp.1405-1408
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• 2012

• 대한한방내과학회지
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• 제32권1호
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• pp.43-55
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• 2011

Objectives : Sokmyeung-tang(SMT) has been used for treatment of CVA in traditional oriental medicine, so this study was designed to evaluate the effect of SMT's protection on brain cell damage against the oxidative stress that was affected by CVA, We also investigated the effect of motor function improvement and neurotrophic factor in ischemic cerebral damaged rats. Methods : We measured cell viability after administrating SMT, chemicals(Paraquat, SNP, rotenone, and $H_2O_2$) which cause oxidative stress, and both SMT and chemicals. We carried out neurobehavioral evaluation(Rotarod test, Beam-walking test, postural reflex test) and observed BDNF (brain-derived neurotrophic factor) expression by injecting SMT into ischemic cerebral damaged rat. Results : Through this study, we observed the following three results. First, brain cell death caused by paraquat, rotenone, and $H_2O_2$ significantly decreased with the treatment of SMT. Second, neuronal movement function in ischemic cerebral damaged rats was significantly improved by the treatment of SMT. Third, BDNF in ischemic cerebral damaged rats increased with the treatment of SMT. Conclusions : SMT protects brain cells from damage induced by oxidative stress (Paraquat, rotenone, $H_2O_2$). SMT also improves neuronal movement function and increases BDNF in ischemic cerebral damaged rats.

• Reproductive and Developmental Biology
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• 제35권4호
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• pp.427-434
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• 2011

Mitochondria diseases have been reported to involve structural and functional defects of complex I-V. Especially, many of these diseases are known to be related to dysfunction of mitochondrial proton-translocating NADH-ubiquinone oxidoreductase (complex I). The dysfunction of mitochondria complex I is associated with neurodegenerative disorders, such as Parkinson's disease, Huntington's disease, and Leber's hereditary optic neuropathy (LHON). Mammalian mitochondrial proton-translocating NADH-quinone oxidoreductase (complex I) is largest and consists of at least 46 different subunits. In contrast, the NDI1 gene of Saccharomyces cerevisiae is a single subunit rotenone-insensitive NADH-quinone oxidoreductase that is located on the matrix side of the inner mitochondrial membrane. The Saccharomyces cerevisiae NDI1 gene using a recombinant adeno-associated virus vector (rAAV-NDI1) was successfully expressed in AML12 mouse liver hepatocytes and the NDI1-transduced cells were able to grow in media containing rotenone. In contrast, control cells that did not receive the NDI1 gene failed to survive. The expressed Ndi1 enzyme was recognized to be localized in mitochondria by confocal immunofluorescence microscopic analyses and immunoblotting. Using digitonin-permeabilized cells, it was shown that the NADH oxidase activity of the NDI1-transduced cells was not affected by rotenone which is inhibitor of complex I, but was inhibited by antimycin A. Furthermore, these results indicate that Ndi1 can be functionally expressed in the AML12 mouse liver hepatocytes. It is conceivable that the NDI1 gene is powerful tool for gene therapy of mitochondrial diseases caused by complex I deficiency. In the future, we will attempt to functionally express the NDI1 gene in mouse embryonic stem (mES) cell.

• Journal of Microbiology and Biotechnology
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• 제30권4호
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• pp.604-614
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• 2020

The application of steroids has steadily increased thanks to their therapeutic effects. However, alternatives are required due their severe side effects; thus, studies on the activities of steroid derivatives are underway. Sugar derivatives of nandrolone, which is used to treat breast cancer, as well as cortisone and prednisone, which reduce inflammation, pain, and edema, are unknown. We linked O-glucose to nandrolone and testosterone using UDP-glucosyltransferase (UGT-1) and, then, tested their bioactivities in vitro. Analysis by NMR showed that the derivatives were 17β-nandrolone β-ᴅ-glucose and 17β-testosterone β-ᴅ-glucose, respectively. The viability was higher and cytotoxicity was evident in PC12 cells incubated with rotenone and, testosterone derivatives, compared to the controls. SH-SY5Y cells incubated with H₂O₂ and nandrolone derivatives remained viable and cytotoxicity was attenuated. Both derivatives enhanced neuronal protective effects and increased the amounts of cellular ATP.

• 한국발생생물학회지:발생과생식
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• 제21권4호
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• pp.417-424
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• 2017

Alzheimer's disease (AD) is neurodegenerative disease, characterized by the progressive decline of memory, cognitive functions, and changes in personality. The major pathological features in postmortem brains are neurofibrillary tangles and amyloid beta ($A{\beta}$) deposits. The majority of AD cases are sporadic and age-related. Although AD pathogenesis has not been established, aging and declining mitochondrial function has been associated. Mitochondrial dysfunction has been observed in AD patients' brains and AD mice models, and the mice with a genetic defect in mitochondrial complex I showed enhanced $A{\beta}$ level in vivo. To elucidate the role of mitochondrial complex I in AD, we used SH-SY5Y cells transfected with DNA constructs expressing human amyloid precursor protein (APP) or human Swedish APP mutant (APP-swe). The expression of APP-swe increased the level of $A{\beta}$ protein in comparison with control. When complex I was inhibited by rotenone, the increase of ROS level was remarkably higher in the cells overexpressing APP-swe compared to control. The number of dead cell was significantly increased in APP-swe-expressing cells by complex I inhibition. We suggest that complex I dysfunction accelerate amyloid toxicity and mitochondrial complex I dysfunction in aging may contribute to the pathogenesis of sporadic AD.

• 농약과학회지
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• 제20권3호
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• pp.197-202
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• 2016

계피 추출물의 지표성분으로 알려진 cinnamaldehyde와 cinnamyl alcohol, 데리스 추출물의 지표성분인 deguelin과 rotenone을 대상으로 유기농업자재 제품 중 안정성을 평가하였다. 시험은 $4^{\circ}C$, $23^{\circ}C$, $35^{\circ}C$, $45^{\circ}C$, $54^{\circ}C$에서 각각 진행하였으며, 계피 추출물을 주성분으로 하는 유기농업자재 중 고상제품(Biopesticide A, B)의 유효성분 반감기가 15.1-46.2 days로 액상제품(Biopesticide C, D)에 비해 보관 중 안정성이 높게 나타났다. 또한, 동일 제품 내에서는 cinnamaldehyde의 안정성이 cinnamyl alcohol보다 높은 것으로 나타났다. 데리스 추출물을 사용한 제품(Biopesticide E, F, G)의 rotenoid계 유효성분 반감기는 1.5-173 days로 제품별 보관온도에 따른 지표성분 안정성이 큰 차이를 나타내었으며, 동일 제품에서 deguelin과 rotenone의 안정성은 큰 차이를 나타내지 않았다.