• The Korean Journal of Physiology and Pharmacology
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• 제26권6호
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• pp.457-468
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• 2022

It has been demonstrated that APPL1 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) is involved in the regulation of several growth-related signaling pathways and thus closely associated with the development and progression of some cancers. Diallyl trisulfide (DAT), a garlic-derived bioactive compound, exerts selective cytotoxicity to various human cancer cells through interfering with pro-survival signaling pathways. However, whether and how DAT affects survival of human hepatocellular carcinoma (HCC) cells remain unclear. Herein, we tested the hypothesis of the involvement of APPL1 in DAT-induced cytotoxicity in HCC HepG2 cells. We found that Lys 63 (K63)-linked polyubiquitination of APPL1 was significantly decreased whereas phosphorylation of APPL1 at serine residues remained unchanged in DAT-treated HepG2 cells. Compared with wild-type APPL1, overexpression of APPL1 K63R mutant dramatically increased cell apoptosis and mitigated cell survival, along with a reduction of phosphorylation of STAT3, Akt, and Erk1/2. In addition, DAT administration markedly reduced protein levels of intracellular TNF receptor-associated factor 6 (TRAF6). Genetic inhibition of TRAF6 decreased K63-linked polyubiquitination of APPL1. Moreover, the cytotoxicity impacts of DAT on HepG2 cells were greatly attenuated by overexpression of wild-type APPL1. Taken together, these results suggest that APPL1 polyubiquitination probably mediates the inhibitory effects of DAT on survival of HepG2 cells by modulating STAT3, Akt, and Erk1/2 pathways.

• 한국환경농학회지
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• 제17권3호
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• pp.220-226
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• 1998

살균제 Metalaxyl 입제, 살충제 Carbofuran 입제, 및 제초제 Simazine수화제를 전주와 익산의 두 포장에서 각각 반량, 기준량, 1.5배량, 2배량을 처리한 결과, 포장에서의 형광 pseudomonads수는 $10^3-10^6/g$까지 분포하였다. 그 중에서도 두 토양의 살충제 처리구에서 많은 균이 출현하였다. 익산 토양의 경우는 처리 7일 후에는 감소하는 경향이었으나 14일째에 살균제 및 제초제 처리구에서 최고치를 나타냈으며, 살균제의 경우는 112일 후에 다시 증가하였다. 전주 토양에서는 7일 후에 최고치를 나타냈고, 살충제 처리구는 꾸준히 증가하여 56일 후에 최고치를 나타냈다. 제초제 처리구는 시간 경과와 함께 서서히 감소하는 경향이었다. 일반 곰팡이 수는 익산 토양에 살균제를 처리하므로서 7일 후에는 감소하였으나 14일 후 56일 후에 최고치를 나타냈다. 살충제 처리구는 28일 후에 약간 감소하였으나 그 외에는 7일 후와 비슷한 수준으로 1.0-8.6 ${\times}\;10^{4}/g$이었고, 제초제 처리구는 마지막 조사 기간인 112일 후에 최고치를 나타냈다. 전주토양에 살균제를 첨가하면 7일 후에는 감소하였으나 56일 후부터는 증가하였다. 살충제 처리로 익산 토양과 마찬가지로 감소하였으나 56일후에는 증가하기 시작하였다. 또 제초제 처리구는 점차적으로 증가되는 경향이었다. 일반 세균은 익산 포장과 전주포장간에 큰 차이는 없었다$(26.6-29.6\;{\times}\;10^{6}/g)$. 그러나 살균제 처리구에서는 28일 후에 급증하여 56일 후에는 최고치를 나타냈다. 살충제 처리구는 서서히 증가하여 살균제 처리와 마찬가지로 56일 후에 최고치를 나타냈으며, 제초제 처리구는 56일 후까지 서서히 증가하였다. 전주토양에서는 3약제 처리구에서 서서히 증가하여 56일 후에 최고치를 나타냈다. 일반 방선균 수는 약제 처리 전에는 익산 포장이 많았고 $(8{\times}10^6/g)$, 두 포장 모두 약제 처리 7일 후에 최고치를 나타냈다가 112일 후 회복되는 경향이었다. 포장조건에서 분리한 형광pseudomonads 104균주 중 P. putida는 10균주, P. fluorescens는 30균주로 간이 동정되었으며, 공시한 104균주 모두 각각의 농약 100ppm씩 첨가한 배지에서 모두 생육이 가능하여 모든 농약에 내성을 나타냈다.

• 전자진흥
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• 제11권3호
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• pp.125-129
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• 1991

• 생물정신의학
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• 제4권1호
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• pp.48-53
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• 1997

CV(bDAT) cell line, expressing dopamine transporter stably, has been established by transfection of CV-1 cells with bovine dopamine transporter cDNA. Using CV(bDAT) cells, the effects of various antipsychotic drugs on dopamine uptake activity were investigated. All of antipsychotic drugs tested, inhibited the [$^3H$]dopamine uptake into CV(bDAT) cells with $IC_{50}s$ in the low to mid micromolar range, implying that antipsychotic drugs may produce overflow of dopamine in the synaptic cleft of dopaminergic neuron.

• 동의신경정신과학회지
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• 제16권1호
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• pp.43-66
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• 2005

Object : This study was designed to asses the protective effects of Kunneo tang on cognitive decline of the patients with early DAT. Method : Before administered with Kunneotang, 16 patients with early DAT were measured by auditory ERP, MMSE-K and K-DRS. During 12 months the patients with early DAT were administered with Kunneotang. After 12months the patients were measured by the same examinations again. Result : 1. The total score of MMSE-K decreased but it was not significant. 2. The total score of K-DRS increased but it was not significant. Among the five criteria(attention, memory, initiation/perseveration, construction, conceptualization), Initiation/perseveration score signifcantly decreased and there were no significant differences in the other scores. But, memory mean score had a tendency to increase. 3. The latency of ERP P300 component increased but it was not significant and the amplitude of ERP P300 component showed the significant difference. Conclusion : The results suggest that Kunneotang may have protective effects on cognitive decline in the patients with early DAT.

• 대한핵의학회지
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• 제38권1호
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• pp.41-51
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• 2004

목적 : 본 연구는 약물에 노출되지 않은 뚜렛 장애 아동들에게 치료 목적으로 일정기간 일정한 용량의 risperidone을 투여한 후 치료 전과 후의 틱증상 척도의 변화 정도와 $[^{123}I]IPT$ SPECT로 측정한 기저 신경절 DAT밀도에 변화가 있는 지 여부를 알아보고자 하였다. 대상 및 방법 :만 $6{\sim}12$세 사이의 아동으로 약물 비노출뚜렛 장애 아동 9명과 11명의 정상 대조군을 대상으로 risperidone 치료 전과 후에서 각각 $[^{123}I]IPT$ SPECT로 측정한 기저 신경절 DAT 밀도에 변화를 정량적 계측하고 치료전 약물 비노출군과 정상대조군의 기저 신경절 DAT 밀도에 차이를 통계적 분석하였으며, 약물 비노출군아동의 치료전과 치료후의 기저 신경절 DAT 밀도에 차이를 통계분석하였다. 결과: 9명의 약물 비노출뚜렛 장애 아동군과 정상 대조군 사이의 좌,우측 기저 신경절 DAT특이결합/비특이결합 비율의 비교한 결과 좌,우측 기저 신경절 모두 DAT특이결합/비특이결합 비율이 정상 대조군에 비해서 증가되어 있었다. (좌측: z=1.576, p=0.043, 우측: z=1.787, p=0.025). 9명의 뚜렛 장애 아동에서 risperidone치료 전과 후 상태에서 기저 신경절 DAT 특이결합/비특이 결합 비율 비교한 결과, risperidone 전후 사이에 유의한 차이가 관찰되지 않았다. (우측: t=-0.974, p=0.362 ; 좌측: t=-0.513, p=0.634). 결론: Risperidone 투여가 뚜렛 장애의 증상을 호전시키는 시점에서 기저 신경절 DAT 밀도는 변화시키지 앓을 수 있음을 제시한다.

• Nuclear Medicine and Molecular Imaging
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• 제41권2호
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• pp.152-157
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• 2007

Imaging of the dopamine transporter (DAT) provides a marker for the integrity of presynaptic nigrostriatal dopaminergic system. DAT density is reduced in Parkinson disease, multiple system atrophy, and progressive supranuclear palsy. In patients with suspicious parkinsonism, normal DAT imaging suggests an alternative diagnosis such as essential tremor, vascular parkinsonism, or drug-induced parkinsonism. DAT imaging is a useful tool to aid clinician's differential diagnosis in parkinsonism.

• 대한핵의학회지
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• 제37권1호
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• pp.34-42
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• 2003

The dopamine transporter (DAT) is responsible for the re-uptake of dopamine from the synaptic cleft and is located on dopaminergic nerve terminals only. DAT single photon emission computed tomography (SPECT) and positron omission tomography (PET) imaging, therefore, offer the unique opportunity to study via striatal uptake the integrity of presynaptic dopaminergic nerve terminals in vivo. In recent years SPECT and PET using specific ligands binding to DAT have evolved as an useful tool for diagnosing and monitoring progression of neurodegenerative disorders affecting dopaminergic systems. This article briefly reviews the literature dealing with DAT SPECT and PET imaging in parkinsonism and other neurodegenerative disorders.

• Journal of Applied Biological Chemistry
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• 제43권3호
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• pp.170-175
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• 2000

A pot-lysimeter experiment was conducted with 3-year-old 'Tsugaru' apple (Malus domestica Borkh) trees to examine the changes in oxygen diffusion rate (ODR) with lateral flow velocity of water through soil. The influence of lateral water flow velocity on water relations and elemental content in leaf, and sap temperature distribution patterns of the xylem of trees were also determined. Trees were grown under four soil water regimes: (1) fast laterally flowing (FWT, $2.50{\times}10^{-4}cm\;s^{-1}$), (2) slow laterally flowing (SWT, $0.25{\times}10^{-4}cm\;s^{-1}$), and (3) stagnant water table (WLT) at 60-cm, and (4) drip-irrigation at -40 kPa of soil matric potential as a control. The rate of $O_2$ diffusion converged near $2{\times}10^{-3}g\;m^{-2}\;min^{-1}$ for FWT and control soils, but decreased below $1{\times}10^{-3}g\;m^{-2}\;min^{-1}$ 40 days after treatment (DAT) for WLT soils. For SWT soils, however, the ODR at 15 cm below the soil surface was similar to that of control, but at 45 cm below the soil surface, ODR was similar to that of the WLT treatment. Leaf water potential of FWT and SWT plants was similar to that of control plants, but the values for SWT plants declined by 98 DAT. Leaf water potential of WLT plants decreased from -1.86 MPa (9 DAT) to -2.41 MPa (59 DAT) and finally down to -2.70 MPa. The sap temperature measured at 1100-hr was lowest at top and highest at bottom for FWT and control plants, but this pattern of SWT and WLT plants was disturbed from 29 DAT. However, for SWT plants, such thermal disturbance of sap temperature disappeared from 63 DAT.

• Genes and Genomics
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• 제40권12호
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• pp.1309-1317
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• 2018

It is well known that dopaminergic genes affect the development of attention deficit hyperactivity disorder (ADHD) in various populations. Many studies have shown that variable number tandem repeats (VNTRs) located within the 3′-untranslated region of DAT1 and in exon 3 of DRD4 are associated with ADHD development; however, these results were inconsistent. Therefore, we investigated the genetic association between two VNTRs and ADHD in Korean children. We determined the VNTRs using PCR. We examined genotype and allele frequency differences between the experimental and control groups, along with the odds ratios, using Chi square and exact tests. We observed a significant association between the children with ADHD and the control group in the 10R/10R genotype of DAT1 VNTRs (p=0.025). In addition, the 11R allele of DAT1 VNTRs showed a higher frequency in the control group than in the ADHD group (p=0.023). Also, the short repeat (without 11R) and long repeat alleles (including 11R) were associated with ADHD (p<0.05). The analysis of DRD4 VNTRs revealed that the 2R allele is associated with ADHD (p=0.025). A significant result was also observed in long and short repeats (p<0.05). Additionally, ADHD subtypes showed that the DRD4 VNTRs are associated with combined and hyperactive-impulsive subtype groups (p<0.05). Therefore, our results suggest that DAT1 VNTRs and DRD4 VNTRs play a role in the genetic etiology of ADHD in Korean children.