• Title/Summary/Keyword:  inhibition

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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.

The Experimental Studies on Anti-bacterial Effect of Tangpo-san on Three species of causative bacteria of Keratitis (탕포산(湯泡散)이 삼종(三種)의 각막염(角膜炎) 유발균들에 미치는 영향)

  • Kang, Sung-Goo;Yoo, Jin-Gon;Choi, Kwan-Ho;Seo, Hyung-Sik
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.19 no.1
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    • pp.1-10
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    • 2006
  • This experimental study was performed to investigate the effect of herbal eye drops, Tangpo-san and Coptidis rhizoma on Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa keratitis. The following results were obtained by using Minimum inhibition Concentration(MIC) and inhibition Zone. 1. MIC on Staphylococcus aureus in Tangpo-san was 100%, in Coptidis rhizoma was 100% and in Cravit was 0.1% 2. MIC on Staphylococcus epidermidis in Tangpo-san was 100%, in Coptidis rhizoma was 10% and in Cravit was 0.1%. 3. MIC on Pseudomonas aeruginosa in Tangpo-san, Coptidis rhizoma was not showing and in Cravit was 0.1%. 4. The size of inhibition zone on Staphylococcus aureus for Tangpo-san was 13.3mm in $50{\mu}{\ell}$, for Coptidis rhizoma was 26mm in $50{\mu}{\ell}$ and for Cravit was 31mm in $50{\mu}{\ell}$, showing the highest antibacterial effect. 5. The size of inhibition zone on Staphylococcus epidermidis for Tangpo-san was 16mm in $50{\mu}{\ell}$, for Coptidis rhizoma was 25mm in $40{\mu}{\ell}$ and for Cravit was 34mm in $50{\mu}{\ell}$, showing the highest antibacterial effect. 6. The size of inhibition zone on Pseudomonas aeruginosa for Tangpo-san, Coptidis rhizoma was not and for Cravit was 24.7mm in $50{\mu}l$, showing the antibacterial effect. In addition, the results shows that the herbal eye drops, Tangpo-san and Coptidis rhizoma can be used to cure Staphylococcus aureus, Staphylococcus epidermidis keratitis and if further study is performed, the use of herbal eye drops will be valuable and beneficial in the clinical medicines.

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Growth Inhibition of Polysaccharide Fraction in Cell Wall Components from Enterococcus faecalis 2B4-1 against Tumor Cell Lines (Enterococcus faecalis 2B4-1 세포벽 성분 중 Polysaccharide Fraction의 종양세포 증식억제 효과)

  • Park, Sang-Jin;Kim, Jeong-Hwan;Lee, Kyung-Ho;Yang, Jong-Beom;Baek, Young-Jin;Kim, Chang-Han
    • Microbiology and Biotechnology Letters
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    • v.27 no.1
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    • pp.8-14
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    • 1999
  • This study was developed to evaluate the growth inhibition effects of cell wall components of Enterococcus faecalis 2B4-1 obtained from feces of neonates against tumor cell lines. Polysaccharide fraction (PS) shown sensitive growth inhibition effect in the cell wall components was isolated and characterized. In growth inhibition effects, residue fractin of whole cell was shown sensitive level of percent survival about 30% when administrated at ehe concentration of 100${\mu}$g/ml, and that was more effective than that of supernatant fraction against the tumor cell lines, SNU-1, 3LL, FARROW and HEC-1-B. Sensitive growth inhibition effects against SNU-1, FARROW and HEC-1-B were performed by whole cell (WC) fraction from Ent. faecalis 2B4-1. Cytoplasm fractin (CP) of WC was shown non-inhibition effect, however, the other part of WC, precipitate of disrupted cell (PD), was sensitive against the tumor cell line mentioned above. Followed by separation to peptidoglycan fraction (PG) and polysaccharide fraction (PS) were all sensitive which the latter was shown more sensitive percent survival than the former. Composed sugars of polysaccharide fraction were determined to D-glucose, L-rhamnose and D-glucosamine, and the rate fo composition was calculated to about 1:1:1 by the data of elemental analysis, IR, TLC and HPLC.

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Inhibition of Acetolactate Synthase from Pea by Pyrimidine Derivatives (Pyrimidine 유도체에 의한 완두 Acetolactate Synthase의 저해에 관한 연구)

  • Joo, Young A;Kim, Dae Whang;Chang, Soo Ik;Choi, Jung Do
    • Journal of the Korean Chemical Society
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    • v.41 no.6
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    • pp.304-312
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    • 1997
  • Acetolactate synthase(ALS) is the common enzyme in the biosynthetic of valine, leucine, and isoleucine, and is the target of several classes of structually unrelated herbicides, including sulfonylureas, imidazolinones, and triazolopyrimidines. In an effort to develop new and desirable herbicides, we have synthesized 4,6-dimethoxypyrimidine derivatives, and examined their inhibitory activities on pea ALS. The most active compound was found to be K11570 and $IC_{50}$ value for K11570 was 0.2 ${\mu}M.$ The inhibition of pea ALS by K11570 was biphasic, showing increased inhibition with incubation time. The K11570 showed mixed-type inhibition with respect to substrate pyruvate. Dual inhibition analysis of K11570 versus sufonylurea herbicide Ally and feedback inhibitor leucine revealed that three inhibitors were competitive for binding to ALS. The arginine modified enzyme showed decreased inhibition by K11570, sufonylurea Ally, and leucine, in constrast to, tryptophan modification did not affect on the sensitivity of ALS to the inhibitors.

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Muscle Eccentric Control in Gait Initiation (보행 시작 시 원심성 근육 수축 조절)

  • Kim, Hyeong-Dong
    • Physical Therapy Korea
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    • v.8 no.4
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    • pp.81-89
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    • 2001
  • There are two independent mechanisms to control the segmental reflex gain in humans during gait. They are presynaptic inhibition and homosynaptic depression. Through the mechanism of the presynaptic inhibition, the muscle spindle afferent feedback can be properly gated during eccentric phase of gait. The modulation of the presynaptic inhibition is reflected in the level of H-reflex at a constant EMG level. During the eccentric muscle activation presynaptic inhibition should increase to account for the lower amplitude level of H-reflex at a constant level of EMG. Homosynaptic depression is another mechanism responsible for regulating the effectiveness of the muscle spindle afferent feedback. Both the presynaptic inhibition and the monosynaptic depression are responsible for modulating reflex gain during gait initiation. Reflex modulation is influenced not only as a passive consequence of the alpha motor neuron excitation level, but also through supraspinal mechanisms. Spastic paretic patients show the impaired soleus H-reflex modulation either during the initial stance phase, or during the swing phase. This abnormal modulatory mechanism can partially and artificially be restored by the application of peripheral stimulus to the sole of the foot, provided that the segmental circuitry remains functional.

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Sensitization of Periodontitis Disease Causing Bacteria by Low Power He-Ne Laser Radiation

  • Satsangi, Akash Tripathi;Mathur, Manish;Saxena, Parul;Prasad, Guru;Shrivastava, Jitendra Nath;Shrivastava, Jenendra Nath;Roy, Sukhdev
    • Journal of Photoscience
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    • v.11 no.32
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    • pp.55-59
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    • 2004
  • The present investigation is an attempt to create an optimized protocol for a bactericidal modality of different powers of He-Ne laser radiation to eliminate periodontitis disease causing bacteria from dental plaques. Periodontitis is most prevalent infectious disease of men and caused by a limited number of Gram negative oral bacteria. Porphyromonas gingivalis and Streptococcus sanguis are the important bacteria responsible for periodontitis diseases. Effect on periodontitis disease causing bacteria were produced by the exposure of different powers of He-Ne laser light i.e. 9 mW, 17 mW and 26 mW of red colour of wavelength 632.8 nm in two different periods of time i.e. 10 min. and 20 min. in the presence of dye Methylene blue (MB) used as a photosensitizer. The results have been shown in terms of percentage inhibition of colony forming units (cfu.) of bacteria. This study has shown that maximum inhibition of cfu. were observed in Laser+MB-20 min. exposure time. This inhibition was followed by Laser+MB-10 min., but minimum inhibition was seen in Laser only at 10 min. exposure. In case of effect of methylene alone on the cfu. of bacteria, it was seen that MB have not shown more inhibition of cfu. and it had shown that the no. of cfu. are very similar to that of control. The above observation of the present study was seen in case of every 3 different type of used powers of laser for both the bacteria. Maximum percentage inhibition of cfu. were seen in case of 26mW powers of He-Ne laser, which was 67. 28% to 61.42% for Porphyromonas gingivalis and Streptococcus sanguis respectively. So, increasing the power of laser (safe range for dentistry is 3-30 mW) under conditions shows an increased percentage inhibition of cfu. Thus the present investigation may be a useful adjunct with mechanical debridement in the prevention of recolonization of subgingival lesions by pathogenic microorganisms which are harmful and drug resistant.

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Study on Inhibition of Platelet Aggregation of Bioactive Constituents from Paeonia lactiflora (작약의 혈소판 응집억제작용에 관한 연구)

  • 박관혁;서범석;손동주;박영현;장성근
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.4 no.4
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    • pp.357-360
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    • 2003
  • Methanol extracts from Paeonia lactiflora showed a strong inhibition against platelet aggregation on platelet activation test. Therefore, the bioactive constituents from Paeonia lactiflora were prepared using chromatography methods and were analyzed by NMR and reference data. Compound 1b was confirmed a same structure with henzoyloxypaeoniflorin, compound 2e was a same structure with paeoniflorin; main product of Paeonia lactiflora. Analytical data of compound 3a were not consistent with any known paeoniflorin soucture, but showed the souctural similarity with it. And also the aggregation inhibition activity of compound 3a showed a strong inhibition($\geq$ 90%) induced by collagen. Therefore it suggested that the structure of compound 3a may be the similar structure of benzoyloxypaeoflorin with a functional group in place of benzoyl group and/or a different functional group in stead of Rl. We suggested that benzoyl group of benzoyloxypaeoniflorin substitued instead of 5-carbon OH group on glycoside moiety paeoniflorin played role of the metabolite in case of a platelet aggregation inhibition activity. Paeoniflorin showed more strong inhibition by thrombin than collagen. Therefore, it may be destructed a calcium metabolite as a forming $Ca^2+$ chelate. Compound 3a may be that other functional group instead of OH group of 5-carbon on glycoside moiety of paeoniflorin and/or OH group of benzoyl moiety of paeoniflorin played role of the metabolite in a platelet aggregation inhibition.

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Synthesis of Polyamine Grafted Chitosan Copolymer and Evaluation of Its Corrosion Inhibition Performance

  • Li, Heping;Li, Hui;Liu, Yi;Huang, Xiaohua
    • Journal of the Korean Chemical Society
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    • v.59 no.2
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    • pp.142-147
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    • 2015
  • Two new chitosan derivatives, polyamine grafted chitosan copolymers have been synthesized for corrosion protection of carbon steel in acidic medium. First, methyl acrylate graft chitosan copolymer (CS-MAA) was prepared by the reaction of chitosan (CS) and methyl acrylate (MAA) via the Michael addition reaction. Then, CS-MAA was reacted with ethylene diamine (EN) and triethylene tetramine (TN) respectively to synthesize ethylene diamine grafted chitosan copolymer (CS-MAA-EN) and triethylene tetramine grafted chitosan copolymer (CS-MAA-TN), and the structures were characterized by Fourier-transform infrared spectroscopy (FT-IR). At last, the corrosion inhibition activities on Q235 carbon steel were investigated by using gravimetric measurements, metallographic microscope, potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) measurements. The compounds CS-MAA-EN and CS-MAA-TN show an appreciable corrosion inhibition property against corrosion of Q235 carbon steel in 5% HCl solution at $25^{\circ}C$. It has been observed that CS-MAA-EN shows greater corrosion inhibition efficiency than CS-MAA-TN. The inhibition efficiency of CS-MAA-EN was close to 90% when the mass fraction concentration was 0.2%~0.3%; the inhibition efficiency of CS-MAA-TN was close to 85% when the mass fraction concentration was 0.02%. The present work provided very promising results in the preparation of green corrosion inhibitors.

Inhibition of Arachidonate Release From Rat Peritoneal Macrophage by Biflavonoids

  • Lee, Song-Jin;Son, Kun-Ho;Chang, Hyeun-Wook;Kang, Sam-Sik;Kim, Hyun-Pyo
    • Archives of Pharmacal Research
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    • v.20 no.6
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    • pp.533-538
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    • 1997
  • Biflavonoid is one of unique classes of naturally-occurring bioflavonoid. Previously, certain biflavonoids were found to possess the inhibitory effects on phospholipase $A_2$ activity and lymphocytes $ proliferation^1$ suggesting their anti-inflammatory/immunoregulatory potential. In this study, effects of several biflavonoids on arachidonic acid release from rat peritoneal macrophages were investigated, because arachidonic acid released from the activated macrophages is one of the indices of inflammatory conditions. When resident peritoneal macrophages labeled with $[^{3}H]$arachidonic acid were activated by phorbol 12-myristate 13-acetate(PMA) or calcium ionophore, A23187, radioactivity released in the medium was increased approximately 4.1-7.3 fold after 120 min incubation compared to the spontaneous release in the control incubation. In this condition, biflavonoids (10 uM) such as ochnaflavone, ginkgetin and isoginkgetin, showed inhibition of arachidonate release from macrophages activated by PMA (32.5-40.0% inhibition) or A23187 (21.7-41.7% inhibition). Amentoflavone showed protection only against PMA-induced arachidonate release, while apigenin, a monomer of these biflavonoids, did not show the significant inhibition up to 10 uM. Staurosporin (1 uM), a protein kinase C inhibitor, showed an inhibitory effect only against PMA-induced arachidonate release (96.8% inhibition). Inhibition of arachidonate release from the activated macrophages may contribute to an anti-inflammatory potential of biflavonoids in vivo.

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Changes of Vastus Medialis Oblique and Vastus Lateralis Muscle Activities During Walking by Different Taping Method (테이핑 방법에 따른 보행 중 안쪽넓은근과 가쪽넓은근의 근활성도 변화)

  • Min-Hyung Rhee;Jong-Soon Kim
    • PNF and Movement
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    • v.21 no.2
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    • pp.231-241
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    • 2023
  • Purpose: Weakness of the vastus medialis oblique muscle (VMO), or the imbalance between VMO and vastus lateralis muscle (VL) activity, is one of the most important factors in knee joint problems. Rigid taping techniques, such as patellar inhibition taping and VL inhibition taping, are frequently used in clinical practice to treat knee joint problems. The purpose of this study was to compare the acute effect of three different types of taping (patellar inhibition taping (PIT), distal VL inhibition taping (DVLIT), and proximal VL inhibition taping (PVLIT)) on electromyography (EMG) activity of VMO, VL, and VMO:VL ratio during walking. Methods: Thirty-eight normal healthy subjects (38 males; mean age = 31.00 years) voluntarily participated in this study. EMG was applied to investigate muscle activation during walking. Repeated measures of ANOVA and one-way ANOVA compared the three different conditions (PIT, DVLIT, and PVLIT) for each variable. Results: VMO and VL activation were significantly increased after PTIT application, and VMO and VL activation were significantly decreased after DVLIT and PVLIT application. The VMO:VL ratio increased after the three types of taping application, but there were no significant differences among the three types of taping. Conclusion: Based on the results of this study, PTIT is more effective than DVLIT and PVLIT in increasing the muscle activation of the VMO and VL during walking. Also, DVLIT is more effective for increasing the VMO:VL ratio and has beneficial effects on the imbalance between VMO and VL activity.