• Animal cells and systems
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• 제11권1호
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• pp.9-15
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• 2007

The naphthoquinone analog (2,3-dichloro-6,9-dihydroxy-1,4-naphtoquinone, NA) has an inhibitory effect on cdc25A protein phosphatase in vitro, which is responsible for G1/S transition during cell cycle. However, the exact mechanism inducing the growth inhibition is not understood. In this study, we investigated the regulatory mechanisms of growth arrest induced by NA, as a new potent inhibitor of cdc25A phosphatase, in human hepatocarcinoma SK-hep-1 cells. We found that NA induced the G1 arrest by perturbation of protein tyrosine dephosphorylation of Cdk2, which may be resulting from inhibition of cdc25A phosphatase. In addition, p21 was expressed in a p53-independent manner and participated in the NA-induced G1 arrest by inhibiting Cdk2 activity. Although the exact mechanism is not known, the p21 expression might be related to MAPK activation. From these results, we suggest that NA induces G1 arrest via inhibition of cdc25A and induction of p53-independent p21 expression in SK-Hep-1 cells.

• 유기물자원화
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• 제19권3호
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• pp.63-72
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• 2011

본 연구에서는 benzalkonium chloride 처리에 따라 바이오가스 생산이 억제되는 정도를 평가하였다. 바이오가스 생산 억제 수준은 10 ppm, 40 ppm, 80ppm의 benzalkonium chloride가 처리되었을 때 각각 10%, 30-40%, 70% 이상이었다. Benzalkonium chloride의 처리에 따라 저해되는 효소를 알아내기 위하여 효소 활성을 분석하였으며 산성/알칼리 포스파타아제, 프로테아제는 메탄 생산량과 음의 상관관계를 나타내었다. ${\alpha}$-글루코시다아제는 실험기간 동안 메탄 생성량과 상대적으로 낮은 음의 상관성을 보였으며(p<0.01, r=-426), 다른 효소와의 상관성도 상대적으로 낮았다. 메탄생성률(ml/day)은 benzalkonium chloride및 산성 포스파타아제와 유의한 상관성을 나타내었다. Benzalkonium chloride가 대장균에 미치는 영향을 원판확산법을 통하여 분석하였다. Benzalkonium chloride의 농도가 높을수록 세균증식 억제대가 확장되었으며, 이를 통하여 benzalkonium chloride가 초산생성균의 증식을 억제함으로써 혐기소화조에 영향을 미칠 수 있다는 것을 확인하였다.

• Archives of Pharmacal Research
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• 제8권4호
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• pp.267-272
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• 1985

Pyrantal pamoate's anthelmintic activity is due to its action as a neuromuscular blocking agent. It is generally well tolerated. Transient rises in SGOT levels have been reported in the drug-treated patients. Decreased levels of serum alkaline phosphatase post treatment were found in yound dogs. The present study was performed to investigate the possible toxic effects of pyrantal pamoate in pregnant mice progenies. The drug was given in different doses to these mothers in the first, second and third trimester. Serum alkaline phosphatase, SGOT and SGPT of one or two month old offspring were monitored. SGOT levels showed an increase in some doses in one and two month old offspring where alkaline phosphatase showed a decrease in some doses in one and two month old offspring. The latter effect may be due to osteoblastic alkaline phosphatase inhibition. The effect on SGOT levels, however, was difficult to explain, but may be due to a toxic effect on liver cells or cardiac muscles.

• 생약학회지
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• 제41권3호
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• pp.227-231
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• 2010

Protein tyrosine phosphatase 1B (PTP1B) is predicted to be therapeutic target in treatment of type 2 diabetes and obesity. Thus, in order to search for PTP1B inhibitors, we screened the inhibitory activity of PTP1B in the water extracts of 84 medicinal herbs. Among them, the extracts of Pini Folium, Magnoliae Cortex, Artemisiae asiaticae Herba, Schizonepetae Herba, Menthae Herba, Mume Fructus, Cimicifugae Rhizoma, and Amomi Cardamomi Fructus showed relatively significant (58-68%) inhibitory activity against PTP1B. Especially, the methylene chloride fraction of the methanol extract of Menthae Herba (81% inhibition at 30 ${\mu}g$/ml) showed more potent inhibitory activity against PTP1B than others.

• Biotechnology and Bioprocess Engineering:BBE
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• 제5권6호
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• pp.418-421
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• 2000

A new direct colorimetric assay of microcystin in water and algal samples is proposed consisting of two procedures as follows: 1) the elimination of phosphorus in the sample and concentration of microcystin using a C(sub)18 cartridge, 2) the detection of the released phosphorus by the ascorbic acid method and determination of protein phosphatase (PP) inhibition by microcystin. The optimum amounts of phosphorylase ${\alpha}$ and PP-1 in 50 ${\mu}$L concentrated sample were 50$\mu\textrm{g}$/50${\mu}$L buffer and 1.0unit/50${\mu}$L buffer, respectively, for the best assay. The pH for the maximum activity of PP-1 was 8. The minimum detectable concentration for this method was about 0.02$\mu\textrm{g}$/L, which is sufficient to meet the proposed guideline level of 1$\mu\textrm{g}$ microcystin/L in drinking water. Consequently, it would seem that the proposed direct colorimetric assay using PP is a rapid, easy, and convenient method for the detection of microcystin in water and algal samples.

• BMB Reports
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• 제34권6호
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• pp.517-525
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• 2001

Six renaturable protein kinases that utilize the myelin basic protein (MBP) as a substrate were activated during prolonged exposure of cardiac myocytes to okadaic acid (OA). We characterized the substrate preference and activation of these kinases, with particular emphasis on 3 novel kinases-MBPK-55, MBPK-62 and MBPK-87. The transcription factors c-Jun, Elk, ATF2, and c-Fos that are used to assess mitogen-activated protein kinase activation were all poor substrates for these three kinases. MAPKAPK2 was also not phosphorylated. In contrast, Histone IIIS was phosphorylated by MBPK-55 and MBPK-62. These protein kinases were activated in cultured cardiac fibroblasts, H9c2 cardiac myoblasts, and Cos cells. High concentrations (0.5 to $1\;{\mu}M$) of OA were essential for the activation of the protein kinases in all of the cell types examined, whereas calyculin A [an inhibitor of protein phosphatase 1 (PP1) and PP2A], cyclosporin A (a PP2B inhibitor), and an inactive OA analog all failed to activate these kinases. The high dose of okadaic acid that is required for kinase activation was also required for phosphatase inhibition, as assessed by immunoblotting whole cell lysates with anti-phosphothreonine antibodies. A variety of chemical inhibitors, including PD98059 (MEK-specific), genistein (tyrosine kinase-specific) and Bisindolylmaleimide I (protein kinase C-specific), failed to inhibit the OA activation of these kinases. Thus, MBPK-55 and MBPK-62 are also Histone IIIS kinases that are widely expressed and specifically activated upon exposure to high OA concentrations.

• 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.

• Bulletin of the Korean Chemical Society
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• 제33권9호
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• pp.3142-3144
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• 2012

• Bulletin of the Korean Chemical Society
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• 제32권6호
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• pp.2135-2136
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• 2011

• Bulletin of the Korean Chemical Society
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• 제34권12호
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• pp.3871-3873
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• 2013