• BMB Reports
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• v.44 no.3
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• pp.182-186
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• 2011

Exogenous stimuli such as nerve growth factor (NGF) exert their effects on neurite outgrowth via Trk neurotrophin receptors. TrkA receptors are known to be ubiquitinated via proteasome inhibition in the presence of NGF. However, the effect of proteasome inhibition on neurite outgrowth has not been studied extensively. To clarify these issues, we investigated signaling events in PC12 cells treated with NGF and the proteasome inhibitor MG132. We found that MG132 facilitated NGF-induced neurite outgrowth and potentiated the phosphorylation of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) and phosphatidylinositol-3-kinase (PI3K)/AKT pathways and TrkA receptors. MG132 stimulated internalization of surface TrkA receptor and stabilized intracellular TrkA receptor, and the $Ub^{K63}$ chain was found to be essential for stability. These results indicate that the ubiquitin-proteasome system potentiated neurite formation by regulating the stability of TrkA receptors.

• Journal of Powder Materials
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• v.1 no.2
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• pp.208-216
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• 1994

A radically new approach to the in situ synthesis of the consituent phases of a composite structure has enabled the production of a new WC/Co materials with an ultrafine microstructure. The process for synthesizing nanophase WC/Co powders consists of spray drying from solution to form a homogeneous precursor powder, and thermochemical conversion of the precursor powder to the nanophase WC/Co powder. Near theoretical density of pure nanophase WC-10 wt%Co has been obtained in only 30 sec at 140$0^{\circ}C$. But WC particles were grown up very rapidly with longer sintering time to get full density. To overcome coarsening of WC particle during sintering, VC, TaC and VC/TaC were used as the grain growth inhibitor with different amount respectively. VC/TaC doped WC-10 wt%Co was shown superior hardness and TRS and microstructure was maintained ultrafine scale (average WC size is less than 0.1 ${\mu}{\textrm}{m}$).

• Journal of Hydrogen and New Energy
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• v.21 no.3
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• pp.220-226
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• 2010

The heat transfer performance improvement in closed cooling water system of an electric power generation can be achieved by a corrosion control using corrosion inhibitors. The effect of trisodium phosphate and sodium nitrite upon carbon steel at various $Cl^{-1}$ ion containing water concentrations was examined by an integrated corrosion monitoring system. Nitrite was found to be the most effective inhibitor among tested inhibitors for carbon steel. The inhibiting process is considered as adsorption of nitrite ions in oxide layer which form a passive film on the carbon steel surface.

• Childhood Kidney Diseases
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• v.6 no.1
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• pp.85-91
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• 2002

Purpose: Phosphodiesterase (PDE) inhibitor increases the cellular content of cAMP, and cAMP suppresses connective tissue growth factor (CTGF) expression induced by TGF-${\beta}1$. Therefore, we investigated whether PDE inhibitor suppresses renal fibrosis without suppression of TGF-${\beta}1$. Materials and Methods : Renal interstitial fibrosis was produced by ligation of left ureter in Sprague-Dawley rats. Cilostazol, a selective PDE3 inhibitor, and dipyridamole, a hybrid PDE5, PDE6, and PDE8 inhibitor, were provided in drinking water for 7 days. In addition to the Masson-trichrome score of renal tissue, the concentration of fibronectin and TGF-${\beta}1$ in renal tissue- conditioned media was measured by ELISA. Results : Masson- trichrome score and fibronectin concentration were significantly lower in cilostazol-treated group compared to the control group (P<0.05). Though dipyridamole treatment seemed to suppress the Masson- trichrome score and fibronectin concentration too, the decrements were not statistically significant. There was no difference in TGF-${\beta}1$ concentration among the groups. Conclusion: A selective PDE3 inhibitor cilostazol suppresses renal fibrosis without alteration of TGF-${\beta}1$ expression. (J Korean Soc Pediatr Nephrol 2002 ;6 : 85-91)

• Korean Journal of Plant Resources
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• v.31 no.3
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• pp.218-227
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• 2018

In this study, we investigated the effect of the extracts from Vaccinium oldhamii on cell proliferation and the regulatory mechanisms of cyclin D1 protein level in human cancer cells. The branch extracts from Vaccinium oldhamii (VOB) showed higher inhibitor effect against the cell growth than leave extracts (VOL) and fruit extracts (VOF) in human colorectal cancer, breast cancer, prostate cancer, non-small lung cancer, pancreatic cancer and liver cancer cells. In addition, VOB decreased cyclin D1 level at both protein and mRNA level. MG132 treatment attenuated VOB-mediated cyclin D1 downregulation. A point mutation of threonine-286 to alanine attenuated cyclin D1 degradation by VOB. In addition, the inhibition of nuclear export by leptomycin B (LMB) attenuated cyclin D1 degradation by VOB. But, the treatment of PD98059 (ERK1/2 inhibitor), SB203580 (p38 inhibitor), SP600125 (JNK inhibitor), LiCl ($GSK3{\beta}$ inhibitor), LY294002 (PI3K inhibitor) or BAY 11-7082 ($I{\kappa}K$ inhibitor) did not affect VOB-induced cyclin D1 degradation. In conclusion, VOB induced cyclin D1 degradation through redistribution of cyclin D1 from the nucleus to cytoplasm via T286 phosphorylation of cyclin D1, which resulted in the inhibition of cancer cell proliferation.

• Molecules and Cells
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• v.26 no.3
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• pp.236-242
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• 2008

Invertase (${\beta}$-D-fructofuranosidase; EC 3.2.1.26) catalyzes the conversion of sucrose into glucose and fructose and is involved in an array of important processes, including phloem unloading, carbon partitioning, the response to pathogens, and the control of cell differentiation and development. Its importance may have caused the invertases to evolve into a multigene family whose members are regulated by a variety of different mechanisms, such as pH, sucrose levels, and inhibitor proteins. Although putative invertase inhibitors in the Arabidopsis genome are easy to locate, few studies have been conducted to elucidate their individual functions in vivo in plant growth and development because of their high redundancy. In this study we assessed the functional role of the putative invertase inhibitors in Arabidopsis by generating transgenic plants harboring a putative invertase inhibitor gene under the control of the CaMV35S promoter. A transgenic plant that expressed high levels of the putative invertase inhibitor transcript when grown under normal conditions was chosen for the current study. To our surprise, the stability of the invertase inhibitor transcripts was shown to be down-regulated by the phytohormone ABA (abscisic acid). It is well established that ABA enhances invertase activity in vivo but the underlying mechanisms are still poorly understood. Our results thus suggest that one way ABA regulates invertase activity is by down-regulating its inhibitor.

• Proceedings of the Korean Magnestics Society Conference
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• 2010.06a
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• pp.165-166
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• 2010

• Biomolecules & Therapeutics
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• v.21 no.2
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• pp.114-120
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• 2013

Most patients with mutant B-Raf melanomas respond to inhibitors of oncogenic B-Raf but resistance eventually emerges. To better understand the mechanisms that determine the long-term responses of mutant B-Raf melanoma cells to B-Raf inhibitor, we used chronic selection to establish B-Raf (V600E) melanoma clones with acquired resistance to the new oncogenic B-Raf inhibitor UI-152. Whereas the parental A375P cells were highly sensitive to UI-152 ($IC_{50}$ < $0.5{\mu}M$), the resistant sub-line (A375P/Mdr) displayed strong resistance to UI-152 ($IC_{50}$ < $20{\mu}M$). Immunofluorescence analysis indicated the absence of an increase in the levels of P-glycoprotein multidrug resistance (MDR) transporter in A375P/Mdr cells, suggesting that resistance was not attributable to P-glycoprotein overexpression. In UI-152-sensitive A375P cells, the anti-proliferative activity of UI-152 appeared to be due to cell-cycle arrest at $G_0/G_1$ with the induction of apoptosis. However, we found that A375P/Mdr cells were resistant to the apoptosis induced by UI-152. Interestingly, UI-152 preferentially induced autophagy in A375P/Mdr cells but not in A375P cells, as determined by GFP-LC3 puncta/cell counts. Further, autophagy inhibition with 3-methyladenine (3-MA) partially augmented growth inhibition of A375P/Mdr cells by UI-152, which implies that a high level of autophagy may protect UI-152-treated cells from undergoing growth inhibition. Together, our data implicate high rates of autophagy as a key mechanism of acquired resistance to the oncogenic B-Raf inhibitor, in support of clinical studies in which combination therapy with autophagy targeted drugs is being designed to overcome resistance.

• Korean Journal of Weed Science
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• v.31 no.2
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• pp.192-198
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• 2011

This study was conducted to investigate the herbicidal activity against Scirpus planiculmis (SCPPL) which has been reported as resistant biotype on sulfonylurea (SU) herbicides at the west coast reclaimed area first and proliferated continuously at Hwasung and Pyeongtaek in Gyeonggi province, and some Chungnam province. In order to investigate resistance breakability against SCPPL, new rice herbicides containing tefuryltrione [p-hydrophenyl pyruvate dioxygenase (HPPD) inhibitor], pyrimisulfan and triafamone[actolactate synthethase (ALS) inhibitor] were tested. In both lab and field experiments, tefuryltrione GR, 4-HPPD inhibitor showed growth retardation with a bleaching on the young leaves of SCPPL at early time after treatment. However, it restored and regerminated with insufficient control effect. On the other hand, pyrimisulfan+mefenacet SC, triafamone+tefuryltrione GR, and ALS inhibitor showed excellent control effect on SU-resistant SCPPL with growth retardation and necrosis. In particular, pyrimisulfan+mefenacet SC showed excellent controlling effect on SU-resistant SCPPL in regional field experiments.

• Molecules and Cells
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• v.21 no.2
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• pp.237-243
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• 2006

Brain-derived neurotrophic factor (BDNF) is a neuromodulator of nociceptive responses in the dorsal root ganglia (DRG) and spinal cord. BDNF synthesis increases in response to nerve growth factor (NGF) in trkA-expressing small and medium-sized DRG neurons after inflammation. Previously we demonstrated differential activation of multiple BDNF promoters in the DRG following peripheral nerve injury and inflammation. Using reporter constructs containing individual promoter regions, we investigated the effect of NGF on the multiple BDNF promoters, and the signaling pathway by which NGF activates these promoters in PC12 cells. Although all the promoters were activated 2.4-7.1-fold by NGF treatment, promoter IV gave the greatest induction. The p38 mitogen-activated protein kinase (MAPK) inhibitor, SB203580, phosphatidylinositol 3-kinase (PI-3K) inhibitor, LY294003, protein kinase A (PKA) inhibitor, H89, and protein kinase C (PKC) inhibitor, chelerythrine, had no effect on activation of promoter IV by NGF. However, activation was completely abolished by the MAPK kinase (MEK) inhibitors, U0126 and PD98059. In addition, these inhibitors blocked NGF-induced phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2. Taken together, these results suggest that the ERK1/2 pathway activates BDNF promoter IV in response to NGF independently of NGF-activated signaling pathways involving PKA and PKC.