• Journal of Life Science
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• v.29 no.12
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• pp.1329-1336
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• 2019

Subventricular zone (SVZ) in the brain contains neural stem cells (NSCs) which self-renew and differentiate to neurons and glial cells during postnatal period and throughout adulthood. Since fate decision to either proliferation or differentiation has to respond to intracellular and extracellular conditions, many intrinsic and extrinsic factors are involved. Among them, mitochondria have been reported to participate in fate decision of NSCs. In our previous report, we showed that long-term treatment of a mitochondrial inhibitor rotenone greatly inhibited neurogenesis. In this study, we examined the effects of short-term treatment of rotenone on SVZ NSCs. We found that (1) even one-day treatment of rotenone significantly reduced neurogenesis and earlier time points seemed to be more sensitive to rotenone, (2) a number of Mash1+ transit amplifying cells was decreased by one-day treatment of rotenone, (3) short-term treatment of rotenone eliminated most of the differentiated Tuj1+ neurons and Olig2+ oligodendrocytes, while glial fibrillary acidic protein (GFAP)+ astrocytes were not affected, and (4) sulfiredoxin 1 (Srxn1) gene expression was increased after one-day treatment of rotenone, indicating activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. All these results confirm that functional mitochondria are necessary during differentiation to neurons or oligodendrocytes as well as maintenance of neurons after differentiation. Also, these data suggest that temporary exposure to mitochondrial inhibitor such as rotenone might have long-term effects on neurogenic potential of NSCs.

• The Korean Journal of Pesticide Science
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• v.16 no.4
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• pp.302-307
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• 2012

This study was carried out to elucidate residual characteristics of environment friendly agricultural material rotenone in chilli pepper and calculate processing factors by drying. The test material was sprayed twice onto chilli peppers at an interval of seven days and then the chilli peppers were harvested at 0, 1, 3, 5 and 7 days after final spray. Limits of quantitation (LOQs) of rotenone in fresh and dried chilli peppers were 0.03 and 0.07 mg/kg, respectively. Recoveries of the test material in fresh and dried chilli peppers ranged from 89.52 to 97.86% and from 85.76 to 91.61%, respectively. As a results of residual material analysis, amounts of rotenone in fresh and dried chilli peppers ranged from 0.03 to 0.39 mg/kg and from 0.07 to 0.75 mg/kg, respectively, representing that the residual amounts of rotenone decreased time-coursely. Processing factors of rotenone in fresh chilli pepper by drying were found to be from 2.03 to 3.13, indicating that the residual concentration of rotenone in dried chilli pepper increased from two to three times by drying. However, the reduction factor of rotenone in fresh chilli pepper by drying ranged from 0.38 to 0.59, representing that some of rotenone in fresh chilli pepper disappeared during the drying process.

• Journal of Life Science
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• v.28 no.12
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• pp.1397-1405
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• 2018

Mitochondria have multiple functions in cells: providing chemical energy, storing cellular $Ca^{2+}$, generating reactive oxygen species, and regulating apoptosis. Through these functions, mitochondria are also involved in the maintenance, proliferation, and differentiation of stem/progenitor cells. In the brain, the subventricular zone (SVZ) is one of the neurogenic regions that contains neural stem cells (NSCs) throughout a lifetime. However, reports on the role of mitochondria in SVZ NSCs are scarce. Here, we show that rotenone, a complex I inhibitor of mitochondria, inhibits the proliferation and differentiation of SVZ NSCs in different ways. In proliferating NSCs, rotenone decreases mitosis as measured through phosphorylated histone H3 detection; moreover, apoptosis is not induced by rotenone at 50 nM. In differentiating NSCs, rotenone blocks neurogenesis and oligodendrogenesis while glial fibrillary acidic protein-positive astrocytes are not affected. Interestingly, in this study there were more cells in the differentiating NSCs treated with rotenone for 4-6 days than in the vehicle control group which was a different effect from the reduced number of cells in the proliferating NSCs. We examined both apoptosis and mitosis and found that rotenone decreased apoptosis as detected by staining cleaved caspase-3 but did not affect mitosis. Our results suggest that functional mitochondria are necessary in both the proliferation and differentiation of SVZ NSCs. Furthermore, mitochondria might be involved in the mitosis and apoptosis that occur during those processes.

• Journal of Korean Neurosurgical Society
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• v.38 no.6
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• pp.456-464
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• 2005

Objective : The authors investigated whether rotenone induces cellular death also in non-dopaminergic neurons and high concentration of potassium ion can show protective effect for non-dopaminergic neuron in case of rotenone-induced cytotoxicity. Methods : Neuro 2A cells was treated with rotenone, and their survival as well as cell death mechanism was estimated using 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium[MTT] assay, Lactate dehydrogenase[LDH] release assay, fluorescence microscopy, and agarose gel electrophoresis. The changes in rotenone-treated cells was also studied after co-treatment of 50mM KCl. And the protective effect of KCl was evaluated by mitochondrial membrane potential assay and compared with the effects of various antioxidants. Results : Neuro 2A cells treated with rotenone underwent apoptotic death showing chromosome condensation and fragmentation as well as DNA laddering. Co-incubation of neuro 2A cells with 50mM KCl prevented it from the cytotoxicity induced by rotenone. Intracellular accumulation of reactive oxygen species[ROS] resulting by rotenone were significantly reduced by 50mM KCl. Potassium exhibited significantly similar potency compared to the antioxidants. Conclusion : The present findings showed that potassium attenuated rotenone-induced cytotoxicity, intracellular accumulation of ROS, and fragmentation of DNA in Neuro 2A cells. These findings suggest the therapeutic potential of potassium ion in neuronal apoptosis, but the practical application of high concentration of potassium ion remains to be settled.

• The Korean Journal of Pesticide Science
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• v.17 no.4
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• pp.302-306
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• 2013

We report the dietary exposure to rotenone in the Korean population and children (1-18) through consumption of lettuce and cucumber. To obtain the residue data, we analyzed using the GC-NPD and HPLC-DAD method. Rotenone residues in samples were as follows; lettuce 0.16-1.15, cucumber < 0.001-0.006. The average dietary intake was determined using result from the 2009 Korea National Health and Nutrition Examination Survey Data. The risk index (RI) was calculated using rotenone residues and dietary intakes. The lettuce and cucumber showed the highest at 18.41%, 0.00, respectively. RI fell below 100 of %RfD showing no risks in these vegetables. Therefore, the risk assessment on the detected rotenone was evaluated as safe level.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.4
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• pp.281-285
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• 2009

Rotenone, a mitochondrial complex I inhibitor, can induce the pathological features of Parkinson's disease (PD). In the present study, naringin, a grapefruit flavonoid, inhibited rotenone-induced cell death in human neuroblastoma SH-SY5Y cells. We assessed cell death and apoptosis by measuring mitogen-activated protein kinase (MAPKs) and caspase (CASPs) activities and by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 4,6-diamidino-2-phenylindole (DAPI) staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. Naringin also blocked rotenone-induced phosphorylation of Jun NH2-terminal protein kinase (JNK) and P38, and prevented changes in B-cell CLL/lymphoma 2 (BCL2) and BCL2-associated X protein (BAX) expression levels. In addition, naringin reduced the enzyme activity of caspase 3 and cleavages of caspase 9, poly (ADP-ribose) polymerase (PARP), and caspase 3. These results suggest that naringin has a neuroprotective effect on rotenone-induced cell death in human neuroblastoma SH-SY5Y cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.438-445
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• 2008

Dodam formula (Dodam) has been used for neurodegenerative disease in Oriental medicine. Dodam is capable of protecting diverse kinds of cells from damage caused by a variety of toxic stimuli. In the present study, we investigated the underlying protective mechanism of Dodam on rotenone-induced cytotoxicity in rat neuroblastoma Neuro-2A cells. Treatment with Neuro-2A cells with rotenone caused the loss of cell viability, and condensation and fragmentation of nuclei, which was associated with the elevation of ROS level, and lipid peroxidation, the increase in Bax/Bcl-2 ratio. Rotenone induced mitochondrial dysfunction characterized by mitochondrial membrane potential loss and cytochrome-c release. These phenotypes induced by rotenone were reversed by pretreatment with Dodam. Our results suggested that major features of rotenone-induced neurotoxicity are partially mediated by mitochondrial dysfunction and oxidative stress, and that Dodam markedly protects Neuro-2A cells from oxidative injury. These data indicated that Dodam might provide a useful therapeutic strategy in treatment of the neurodegenerative diseases caused by oxidative injuries.

• Korean Journal of Environmental Agriculture
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• v.34 no.1
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• pp.52-56
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• 2015

BACKGROUND: Three commercial biopesticides containing derris extract, which is permitted as a commercial biopesticide substances by the Environmentally-friendly Agriculture Promotion Act, have been marketed in Korea. But, the quantitative analytical method of active substances for crop protection in biopesticides containing derris extract has not known. METHODS AND RESULTS: Solid phase extraction (SPE) cartridge clean-up method for the quantitative analysis of rotenone and deguelin in biopesticides containing derris extract was developed and validated by ultra-performance liquid chromatography (UPLC). The clean-up method was established using hydrophilic lipophilic balance (HLB) SPE cartridges for the bioactive substances in biopesticides containing derris extract, and the eluate was analyzed to quantify the rotenone and deguelin by the UPLC. LOQ and recovery rates of rotenone and deguelin were 0.085 and 0.044 mg/L, 95.7 and 93.3%, respectively. The content of rotenone and deguelin in three biopesticides containing derris extract were analyzed by the developed method, the results showed 0.001-0.236 and

• Korean Journal of Plant Resources
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• v.22 no.6
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• pp.546-551
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• 2009

We examined the growth characteristics, fresh tuber yield, rotenone content of two yam beans (Pachyrhizus erosus and P. ahipa) introduced from Mexico. P. erosus species showed better adaptable ability than P. ahipa species in seed productivity and tuber yield. Rotenone content in the P. erosus species extracted with chloroform was 3.6 folds much more extracted than ethanol extraction. The order of rotenone content found in crude extract obtained by different solvent extraction from the highest to the lowest was mature seed (484.7 ${\mu}g$) and leaves (17.2 ${\mu}g$) of the P. erosus species, respectively.

• YAKHAK HOEJI
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• v.57 no.2
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• pp.77-86
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• 2013

The neuroprotective effects of herbal ethanol extract (GP-EX) from Gynostemma pentaphyllum on dopamine neurons in animal model of Parkinson's disease (PD) were investigated. Rats and mice were administered with rotenone (2.5 mg/kg) for 28 days and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg) for 5 days for the PD models, respectively and the animals were simultaneously treated with GP-EX (30 mg/kg, daily). After preparing the PD models, the animals were also administered with L-DOPA (10 mg/kg) for 14 days with or without GP-EX treatment. Treatment with GP-EX (30 mg/kg) inhibited the rotenone- and MPTP-induced neurotoxic effects in dopamine neurons of rats or mice, which was determined by the numbers of tyrosine hydroxylase-immunohistochemical staining survival cells, as well as the levels of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid. GP-EX (30 mg/kg) also showed the protective effects on neurotoxicity which was induced by long-term administration of L-DOPA (10 mg/kg) in rotenone- and MPTP-induced animal model of PD. The used doses of GP-EX (30 mg/kg) did not produce any signs of toxicity, such as weight loss, diarrhea, or vomiting, in rats and mice during the treatment periods. These results suggest that GP-EX has the protective functions against chronic L-DOPA-induced neurotoxic reactions in dopamine neurons of rotenone- and MPTP-induced animal model of PD. Therefore, the natural GP-EX may be beneficial in the prevention of PD progress and L-DOPA-induced neurotoxicity in PD patients.