• Title/Summary/Keyword: rotenone

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Neuroprotective Effects of Protein Tyrosine Phosphatase 1B Inhibition against ER Stress-Induced Toxicity

  • Jeon, Yu-Mi;Lee, Shinrye;Kim, Seyeon;Kwon, Younghwi;Kim, Kiyoung;Chung, Chang Geon;Lee, Seongsoo;Lee, Sung Bae;Kim, Hyung-Jun
    • Molecules and Cells
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    • v.40 no.4
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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.

Determination of Lethal Concentrations and Lethal Times of Extracts from Tanacetum cineariaiaefolium, Derris elliptica, and Sophora flavescens, to Control Green Peach Aphid, Myzus persicae (복숭아혹진딧물, Myzus persicae, 방제를 위한 제충국, 데리스, 고삼 추출물의 살충농도와 살충시간 결정)

  • Ka Hee Cho;Hyo Jung Kim;Song Hee Han;Young Cheol Kim
    • Korean journal of applied entomology
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    • v.62 no.4
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    • pp.267-275
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    • 2023
  • Botanical extracts are employed in management of aphids. Extracts from Tanacetum cineariaiaefolium, Derris elliptica, and Sophora flavescens are widely used to control various insects. In this study, we determined concentrations of insecticidal active ingredients in commercial botanical extracts of these plants, and we investigated the time and concentration for lethal results with the green peach aphid, Myzus persicae. The concentrations of active ingredients, pyrethrins from T. cineariaiaefolium, rotenone from D. elliptica, and matrine and oxymatrine from S. flavescens, were determined after their fractionation by liquid chromatography followed by mass analysis and comparison with standard compounds. The extracts were tested for lethality in a bioassay with green peach aphids. Sprays at defined doses were applied to tobacco leaves infested with aphid nymphs. The lethal concentrations (LC50) were 20.4 ppm for pyrethrins, 34.1 ppm for rotenone, and 29.6 ppm for matrine at 48 h after treatments. At 100 ppm application levels, the lethal time LT50 was 13.4 h for pyrethrin, 15.1 h for rotenone, and 14.4 h for matrine. Kaplan-Meier analysis indicated the lethal times for the three botanical extracts at 100 ppm were significantly faster than application of a chemical insecticide, Sulfoxaflor, applied at the recommended level. These results provide baselines to develop and formulate single or mixed preparations containing botanical extracts to control green peach aphids on commercial crops.

Functional Expression of the Internal Rotenone-Insensitive NADH-Quinone Oxidoreductase (NDI1) Gene of Saccharomyces cerevisiae in Human HeLa Cells

  • Seo, Byoung-Boo
    • Journal of Embryo Transfer
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    • v.25 no.1
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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.

Effects of Eriobotryae Folium as Anti-Oxidant on HaCaT keratinocyte (비파엽(枇杷葉) 에탄올 추출물이 인간 유래 정상 피부 세포에 미치는 항산화 효과)

  • Park, Yoon-Hee;Kim, Jong-Han;Choi, Jeong-Hwa;Park, Soo-Yeon
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.22 no.3
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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.

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Effects of Sokmyeung-tang(SMT) on the Protection of C6 Glial Cells and Ischemic Brain Damage (속명탕(續命湯)이 C6 glial cell 보호 및 허혈성 뇌손상에 미치는 영향)

  • An, Ga-Yong;Choi, Eun-Hee;Kim, In-Soo;Kang, Seong-Sun;Lee, Young-Soo;Hong, Seok;Jeon, Sang-Yun
    • The Journal of Internal Korean Medicine
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    • v.32 no.1
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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.

Functional Expression of Saccharomyces cerevisiae NADH-quinone Oxidoreductase (NDI1) Gene in the AML12 Mouse Liver Hepatocytes for the Applying Embryonic Stem Cell

  • Seo, Byoung-Boo;Park, Hum-Dai
    • Reproductive and Developmental Biology
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    • v.35 no.4
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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.

Enzymatic Synthesis of Anabolic Steroid Glycosides by Glucosyltransferase from Terribacillus sp. PAMC 23288

  • Yu, Eun-Ji;Yamaguchi, Tokutaro;Lee, Joo-Ho;Lim, A-Rang;Lee, Jun Hyuck;Park, Hyun;Oh, Tae-Jin
    • Journal of Microbiology and Biotechnology
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    • v.30 no.4
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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.

Mitochondrial Complex I Inhibition Accelerates Amyloid Toxicity

  • Joh, Yechan;Choi, Won-Seok
    • Development and Reproduction
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    • v.21 no.4
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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.

The Shelf-life of Agricultural Organic Materials Containing Cinnamon or Derris Extract: Thermal Stability of Cinnamyl Derivatives and Rotenoids (계피 또는 데리스 추출물을 주원료로 하는 유기농업자재의 약효 성분 안정성)

  • Choi, Geun-Hyoung;Jin, Cho-Long;Park, Byung-Jun;Lim, Sung-Jin;Rho, Jin-Ho;Moon, Byung-Cheol;Kong, Seung-Heon;Kim, Jin Hyo
    • The Korean Journal of Pesticide Science
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    • v.20 no.3
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    • pp.197-202
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    • 2016
  • The stabilities of bioactive compounds in cinnamon or derris extract were investigated in commercial agricultural organic materials (biopesticide) during storage on different temperature conditions ($0^{\circ}C$, $23^{\circ}C$, $35^{\circ}C$, $45^{\circ}C$, and $54^{\circ}C$). The selected bioactive compounds were cinnamaldehyde, and cinnamyl alchol in cinnamon extract and deguelin, and rotenone in derris extract. Half-lives of the total cinnamyl derivatives in biopesticide (A, B, C, and D) ranged from 15.1 to 46.2 days on the different temperature and cinnamaldehyde was more stable than cinnamyl alcohol in the biopesticide. The half-lives of total rotenoid ranged from 1.7 to 173 days on the different temperature in the tested biopesticide (E, F, and G) containing derris extract. The stabilities of deguelin, and rotenon in the biopesticide showed similar values in the same condition.