• The Korean Journal of Physiology and Pharmacology
• /
• v.26 no.6
• /
• pp.457-468
• /
• 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.

• Korean Journal of Environmental Agriculture
• /
• v.17 no.3
• /
• pp.220-226
• /
• 1998

The effects of metalaxyl(granule), carbofuran(granule) and simazine(water soluble powder) on the soil microflora were conducted at field soil between Iksan and Chonju province. Pesticides were divided into 0.5, 1, 1.5 and 2.0 times of normal of field, respectively. The number of fluorescent Pseudomonas was ranged from $10^3$ to $10^6/g$ in both field soil treated with cabofuran. Pseudomonas concentration of Chonju field soil slowly increased and approached the maximum level at 56 day after treatment(DAT). It showed the higher at 14DAT than other DAT in Iksan field soil treated with metalaxyl or simazine, whereas it increased again at 112 DAT in metalaxyl treatment. Cabofuran treatment of both field soil showed maximum Pseudomonas number at 28 DAT compared to that of other treatments. In Chonju field soil, those Pseudomonads of metalaxyl and simazine treatment increased the highest level at 7 DAT. Simazine treatment decreased it's number from the beginning of experiment. In both soil, metalaxyl treatment decrease the general fungi number at 7 DAT, but increase at 14 and 56 DAT in Iksan field soil. However it increased at 56 DAT in Chonju field soil. Cabofuran treatment of Iksan field soil tended to decrease general fungi number at 28 DAT, but was ranged from 1.0 to $8.6{\times}104/g$ for the rest of experimental period. It started to increase at 56 DAT simazine treatment of Iksan. General bacterial concentration both soil treated with cabofuran was belong to $26.6{\sim}29.6{\times}106$. It was the highest at 56 DAT, but was not significantly different. General actinomyces number was highly increased at 7 and 112 DAT compared to that of other DAT. Pseudomonas putida or P. fluorescens from both field soil was separated and identified 10 to 30 of all 104 Pseudomonas, respectively. All isolated microorganisms showed chemical resistance of 100ppm metalaxyl, cabofuran and simazine treatment.

• Journal of Korean Electronics
• /
• v.11 no.3
• /
• pp.125-129
• /
• 1991

• Korean Journal of Biological Psychiatry
• /
• v.4 no.1
• /
• pp.48-53
• /
• 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.

• Journal of Oriental Neuropsychiatry
• /
• v.16 no.1
• /
• pp.43-66
• /
• 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.

• The Korean Journal of Nuclear Medicine
• /
• v.38 no.1
• /
• pp.41-51
• /
• 2004

PURPOSE: Tourette's disorder (TD), which is characterized by multiple waxing and waning motor tics and one or more vocal tics, is known to be associated with abnormalities in the dopaminergic system. To testify our hypothesis that risperidone would improve tic symptoms of TD patients through the change of the dopaminergic system, we measured the dopamine transporter (DAT) densities between drug-naive children with TD and normal children, and investigated the DAT density before and after treatment with risperidone in drug-naive children with TD, using iodine-123 labelled $N-(3-iodopropen-2-yl)-2{\beta}-carbomethoxy-3beta-(4-chlorophenyl)tropane$ ($[^{123}I]IPT$) single photon omission computed tomography (SPECT). MATERIALS and METHODS: $[^{123}I]IPT$ SPECT Imaging and Yale Global Tic Severity Scale-Korean version (YGTSS-K) for assessing the tic symptom severity were carried out before and after treatment with risperidone for 8 weeks in nine drug-naive children with TD. Eleven normal children also underwent SPECT imaging 2 hours after an intravenous administration of $[^{123}I]IPT$. RESULTS: Drug-naive children with TD had a significantly greater increase in the specific/nonspecific DAT binding ratio of both basal ganglia compared with the normal children. However, no significant difference in the specific/nonspecific DAT binding ratio of the basal ganglia before and after treatment with risperidone in children with TD was found, although tic symptoms were significantly improved with risperidone. CONCLUSION: These findings suggest that DAT densities are directly associated with the pathophysiology of TD, however, that the effect of risperidone on tic symptoms in children with TD is not attributed to the change of dopaminergic system.

• Nuclear Medicine and Molecular Imaging
• /
• v.41 no.2
• /
• pp.152-157
• /
• 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.

• The Korean Journal of Nuclear Medicine
• /
• v.37 no.1
• /
• pp.34-42
• /
• 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
• /
• v.43 no.3
• /
• pp.170-175
• /
• 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
• /
• v.40 no.12
• /
• pp.1309-1317
• /
• 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.