• Journal of Life Science
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• v.26 no.7
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• pp.826-834
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• 2016

The present investigation was undertaken to examine the effectiveness of the combination treatment of an Hsp90 inhibitor and a SIRT1 inhibitor on suppressing the growth of chemo-resistant human cancer cells. We showed that inhibition of SIRT1 effectively potentiated the cytotoxicity of 17-allylamino-17-demethoxygeldanamycin (17-AAG) and reversed Hsp90 inhibitor resistance in multidrug-resistant (MDR) human ovarian HeyA8-MDR cells. Amurensin G, a potent natural SIRT1 inhibitor, enhanced Hsp90 inhibitor-mediated abrogation of the Hsp90 chaperone function and accelerated degradation of mutated p53 (mut p53), an Hsp90 client protein, by up-regulation of ubiquitin ligase CHIP. Knock-down of CHIP significantly attenuated amurensin G-induced mut p53 degradation. Down-regulation of mut p53 reduced the expression of heat shock factor1 (HSF1)/heat shock proteins (Hsps), a major cause of Hsp90 inhibitor resistance, which led to sensitization of the MDR cells to the Hsp90 inhibitor by the SIRT1 inhibitor. Amurensin G potentiated cytotoxicity of the Hsp90 inhibitor in HeyA8-MDR cells through suppression of 17-AAG-induced Hsp70 and Hsp27 induction via down-regulation of mut p53/HSF1, and it caused activation of PARP and inhibition of Bcl-2. Our data suggests that SIRT1 inhibitors could be used to sensitize MDR cells to Hsp90 inhibitors, possibly through suppression of the mut p53/HSF1-dependent pathway, and a novel mut p53-directed action of SIRT1 inhibition could effectively prevent mut p53 accumulation in MDR cells.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.29 no.5
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• pp.620-628
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• 1996

To avoid the self-agglutination of Staphylococcus aureus sensitized with rabbit antibody in the absence of antigen, we determined the optimum concentration of rabbit antibody for sensitization. It was analyzed by using three different kinds of S. aureus strains at various concentraions of antibody. The optimized coagglutination test using the S. aureus sensitized with rabbit antibody was applied to the diagnosis of edwardsiellosis in field and in laboratory. The presence of E. tarda as low as $10\;{\mu}g/ml$ was detected by this method. Moreover, it showed good coagglutination results against several different forms of antigens such as FKC, EDTA or heat extracted antigen of E. tarda. E. tarda strains, isolated from the flounders suffering from edwardsiellosis in fields, showed some cross-reactions to the E. tarda 219 analyzed by both agglutination and coagglutination test with rabbit anti-E, tarda 219 antibody. The degree of cross-reactions analyzed was enough to apply the coagglutination test for the diagnosis of edwardsiellosis in field. Thus, even 1,000 fold diluted tissue homogenate of infected flounder naturally contained enough E. tarda as an antigen to show good coagglutination with S. aueus sensitized with rabbit anti-E, tarda 219 antibody. The successful application of this method to the homogenate and heat extract of tissues from naturally or artificially infected flounder or tilapia preyed that coagglutination test was a simple and rapid reliable dignostic technique suitable for using in laboratory and field without any special equipments.

• Corrosion Science and Technology
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• v.13 no.3
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• pp.112-119
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• 2014

In this work, it is aimed to develop the fabrication method of axial stress corrosion cracking (SCC) defects having various sizes, on the outer diameter surface of the steam generator (SG) tubings. To control the length of the artificial SCC defect, the specific area of the SG tubing samples was exposed to an acidic solution after a sensitization heat treatment. During the exposure to an acidic solution, a direct current potential drop (DCPD) method was adopted to monitor the crack depth. The size of the SCC defect was first evaluated by an eddy current test (ECT), and then confirmed by a destructive examination. From the comparison, it was found that the actual crack length was well controlled to be similar to the length of the surface exposed to an acidic solution (5, 10, 20 or 30 mm in this work) with small standard deviation. From in-situ monitoring of the crack depth using the DCPD method, it was possible to distinguish a non-through wall crack from a through wall crack, even though the depth of the non-through wall crack was not able to be precisely controlled. The fabrication method established in this work was useful to simulate the SCC defect having similar size and ECT signals as compared to the field cracks in the SG tubings of the operating Korean PWRs.

• Journal of Sensor Science and Technology
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• v.30 no.2
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• pp.94-98
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• 2021

In this study, pure and Co3O4/CoFe2O4-loaded Indium oxide (In2O3) nanofibers were synthesized by the electrospinning of an Indium/Polyvinylpyrrolidone precursor solution containing cobalt and iron bimetallic zeolitic imidazolate frameworks and subsequent heat treatment. The ethanol, toluene, p-xylene, benzene, carbon monodxide, and hydrogen gas sensing characteristics of the solution were measured at 250-400 ℃. 0.5 at%-Co3O4/CoFe2O4-loaded In2O3 nanofibers exhibited extreme response (resistance ratio - 1) to 5 ppm of ethanol (210.5) at 250 ℃ and excellent selectivity over the interfering gases. In contrast, pure In2O3 nanofibers exhibited relatively low responses to all the analyte gases and low selectivity above 250-400 ℃. The superior response and selectivity toward ethanol is explained by the catalytic roles of Co3O4 and CoFe2O4 in gas sensing reaction and the electronic sensitization induced by the formation of p (Co3O4/CoFe2O4)-n (In2O3) junctions.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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• pp.39-48
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• 2023

Spinal nerve injury causes mechanical allodynia and structural imbalance of neurotransmission, which were typically associated with calcium overload. Storeoperated calcium entry (SOCE) is considered crucial elements-mediating intracellular calcium homeostasis, ion channel activity, and synaptic plasticity. However, the underlying mechanism of SOCE in mediating neuronal transmitter release and synaptic transmission remains ambiguous in neuropathic pain. Neuropathic rats were operated by spinal nerve ligations. Neurotransmissions were assessed by whole-cell recording in substantia gelatinosa. Immunofluorescence staining of STIM1 with neuronal and glial biomarkers in the spinal dorsal horn. The endoplasmic reticulum stress level was estimated from qRT-PCR. Intrathecal injection of SOCE antagonist SKF96365 dose-dependently alleviated mechanical allodynia in ipsilateral hind paws of neuropathic rats with ED₅₀ of 18 ㎍. Immunofluorescence staining demonstrated that STIM1 was specifically and significantly expressed in neurons but not astrocytes and microglia in the spinal dorsal horn. Bath application of SKF96365 inhibited enhanced miniature excitatory postsynaptic currents in a dosage-dependent manner without affecting miniature inhibitory postsynaptic currents. Mal-adaption of SOCE was commonly related to endoplasmic reticulum (ER) stress in the central nervous system. SKF96365 markedly suppressed ER stress levels by alleviating mRNA expression of C/ EBP homologous protein and heat shock protein 70 in neuropathic rats. Our findings suggested that nerve injury might promote SOCE-mediated calcium levels, resulting in long-term imbalance of spinal synaptic transmission and behavioral sensitization, SKF96365 produces antinociception by alleviating glutamatergic transmission and ER stress. This work demonstrated the involvement of SOCE in neuropathic pain, implying that SOCE might be a potential target for pain management.

• Journal of Advanced Marine Engineering and Technology
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• v.33 no.8
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• pp.1162-1169
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• 2009

Two kinds of welding methods were carried out for 22APU stainless steel, one is a Laser welding and the other is the TIG welding. In this case, difference of corrosion characteristics of welded zone with two welding methods mentioned above was investigated with electrochemical methods such as measurement of corrosion potential, polarization curves and cyclic voltammogram etc.. Vickers hardness of all welded zone (WM:Weld Metal, HAZ:Heat Affected Zone, BM:Base Metal)in the case of Laser welding showed a relatively higher value than those of TIG welding. Futhermore their corrosion current density in all welding zone were also observed with a lower value compared to TIG welding. In particular corrosion current density of BM regardless of welding method indicated the lowest value than those of other welding zone. Intergranular corrosion was not observed at the corroded surface of all welding zone in the case of Laser welding, however it was observed at WM and HAZ with TIG welding, which is suggested that chromiun depletion due to forming of chromium carbide appears to WM and HAZ which is in the range of sensitization temperature. Therefore their zone can easily be corroded with more active anode. Consequently we can see that corrosion resistance of all welding zone of 22APU stainless steel can apparently be improved by using of Laser welding.

• Journal of Life Science
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• v.28 no.10
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• pp.1212-1219
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• 2018

The critical role of heat shock protein 90 (Hsp90) in tumorigenesis led to the development of several first- and second-generation Hsp90 inhibitors, which have demonstrated promising responses in cancers. In this study, we found second-generation Hsp90 inhibitor BIIB021-resistant multidrug-resistant (MDR) human cancer cells, although BIIB021 was shown to be active in first-generation Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG)-resistant MDR cells. MCF7-MDR and HeyA8- MDR cells were more resistant to BIIB021 than their parental counterparts, indicating that BIIB021 cannot be applicable to all cancer cells expressing MDR proteins. We revealed that dimethyl-celecoxib (DMC), one of the non-steroidal anti-inflammatory drugs (NSAIDs), potentiated cytotoxicity of BIIB021 against both BIIB021-resistant and BIIB021-sensitive MDR cells. The effectiveness of NSAIDs involving celecoxib and DMC in combination with BIIB021 led to the autophagic degradation/down-regulation of mutant p53 (mutp53) that overexpressed MDR cells and the suppression of Hsp70 induction. This resulted in sensitization of MDR cells to BIIB021. Moreover, autophagy induction by sulindac sulfide, another type of NSAID, and niclosamide, an FDA-approved anthelmintic drug, potentiated 17-AAG-mediated autophagic degradation/down-regulation of mutp53 and c-Myc, client proteins of Hsp90. Therefore, our results suggest that NSAIDs and niclosamide positively enhance the anticancer activity of Hsp90 inhibitors through an autophagic pathway. They may also be new candidates for sensitizing MDR cells to Hsp90 inhibitors.

• The Korean Journal of Pain
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• v.13 no.2
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• pp.164-174
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• 2000

Background: After an injury to tissue such as the skin, hyperalgesia develops. Hyperalgesia is characterized by an increase in the magnitude of pain evoked by noxious stimuli. It has been postulated that in the mechanism of hyperalgesia (especially secondary hyperalgesia) and allodynia, a sensitization of central nervous system such as spinal dorsal horn may contribute to development of hyperalgesia. However, the precise mechanism is still unclear. In the present study, we investigated the roles of N-methyl-D-aspartate (NMDA) receptor and nitric oxide (NO) system in the mechanism of hyperalgesia, and their relations with c-fos expression Methods: Inflammation was induced by injection of complete Freund adjuvant (CFA) into unilateral hindpaw of Sprague-Dawley rat. Behavioral studies measuring paw withdrawal responses by von Frey filaments and paw withdrawal latencies by radiant heat stimuli and stainings of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and c-fos immunoreactivity were performed. The effects of MK-801, an NMDA receptor blocker and $N^\omega$-nitro-L-arginine (L-NNA), a nitric oxide synthase (NOS) inhibitor were evaluated. Results: 1) Injection of CFA induced mechanical allodynia, mechanical hyperalgesia and thermal hyperalgesia. And it increased the number of NADPH-diaphorase positive neurons and c-fos expression neurons. 2) MK-801 inhibited mechanical hyperalgesia and thermal hyperalgesia induced by CFA and reduced the number of NADPH-diaphorase positive neurons and c-fos expression neurons. 3) L-NNA inhibited the thermal hyperalgesia and reduced the number of NADPH-diaphorase positive neurons, but did not affect the number of c-fos expression neurons. Conclusions: These results suggest that in the mechanism of mechanical hyperalgesia, NMDA receptor but not NO-system is involved and in the case of thermal hyperalgesia both NMDA receptor and NO system are involved. NO system did not affect the expression of c-fos, but c-fos expression and NOS activity were dependent on the activity of NMDA receptor.