• Animal cells and systems
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• v.14 no.1
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• pp.1-10
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• 2010

Previously we showed that CHIP, a co-chaperone of Hsp70 and E3 ubiquitin ligase, can promote the degradation of mutant SOD1 linked to familial amyotrophic lateral sclerosis (fALS) via a mechanism not involving SOD1 ubiquitylation. Here we present evidence that CHIP functions in the interaction of mutant SOD1 with 26S proteasomes. Bag-1, a coupling factor between molecular chaperones and the proteasomes, formed a complex with SOD1 in an hsp70-dependent manner but had no direct effect on the degradation of mutant SOD1. Instead, Bag-1 stimulated interaction between CHIP and the proteasome-associated protein VCP (p97), which do not associate normally. Over-expressed CHIP interfered with the association between mutant SOD1 and VCP. Conversely, the binding of CHIP to mutant SOD1 was inhibited by VCP, implying that the chaperone complex and proteolytic machinery are competing for the common substrates. Finally we observed that mutant SOD1 strongly associated with the 19S complex of proteasomes and CHIP over-expression specifically reduced the interaction between S6/S6' ATPase subunits and mutant SOD1. These results suggest that CHIP, together with ubiquitin-binding proteins such as Bag-1 and VCP, promotes the degradation of mutant SOD1 by facilitating its translocation from ATPase subunits of 19S complex to the 20S core particle.

• Tribology and Lubricants
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• v.27 no.3
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• pp.134-139
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• 2011

The mechanical equipments which are exposed to impure environment undergo significant reductions in their own lifetimes. Several environmental test procedures have been developed to analyze these phenomena. Moreover in the industry to require shorter development duration, accelerated life testers artificially add test containments into machines. In this research JIS Z 8901 test powder was added into internal gear pumps which are used as oil pumps in vehicles and thus the effects of the addition on the degradation of the pumps were examined. Three kinds of contaminants were selected. Two of the contaminants are identical in particle size but different in the composition of the ingredients. The other pair have identical ingredients and composition but different particle size. The quantity of contaminants was also an interesting factor in this study. The results show that each JIS contaminant caused notable degradation in the discharge flow characteristic of pumps while friction torque degradation did not have any tendency. Finally leakage rates were deduced and equivalent wear volume ratios were calculated.

• Journal of Applied Reliability
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• v.9 no.4
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• pp.275-290
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• 2009

This paper considers accelerated thermal degradation tests which are performed for rubber seal materials used for undersea tunnels constructed by immersion method. Three types of rubber seals are tested; rubber expansion seal, omega seal, and shock absorber hose. Main ingredient of rubber expansion seal is EPDM(Ethylene Propylene Diene Monomer) and that of both omega seal and shock absorber hose is SBR(Styrene Butadiene Rubber). The accelerated stress is temperature and an Arrhenius model is introduced to describe the relationship between the lifetime and the stress. From the accelerated degradation tests, dominant failure mode of the rubber seals is found to be the loss of elongation. The lifetime distribution and the service life of the rubber seals at use condition are estimated from the test results. The acceleration factor for three types of rubber seals are also investigated.

• KSBB Journal
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• v.26 no.5
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• pp.433-438
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• 2011

These studies were conducted to investigate the alcohol degradation effects of the extract of herbal composition (DTS20) containing Viscum album L., Lycium chinense L., Inonotus obliquus and Acanthopanax senticosus H., on the alcohol administered mice. To investigate anti-hangover effect, alcohol and alcohol dehydrogensae (ADH) concentration of blood were measured after oral administration of ethanol. The administration of DTS20 (200-500 mg/kg) had beneficial actions toward alcohol degradation in acute alcohol treated mice model. The oral administration of DTS20 showed decreased gastric mucous membrane damage produced in ethanol treated mice. In addition, intraperitoneal administration of DTS20 showed anti-inflammatory effects in inhibition tests of vascular permeability produced by acetic acid. DTS20 also reduced the concentration of nitric oxide (NO), tumor necrosis factor (TNF)-${\alpha}$ in macrophages that were activated by LPS. These results demonstrate that DTS20 possesses potential to stimulate the alcohol degradation and inhibit the inflammatory effects in mice.

• Fibers and Polymers
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• v.5 no.4
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• pp.289-296
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• 2004

The kinetic parameters, including the activation energy E, the reaction order n, and the pre-exponential factor Z, of the degradation of the copolymers based on the poly(L-lactide) (PLLA) or poly(p-dioxanone-co-L-lactide) (PDO/PLLA) and diol-terminated poly(ethylene glycol) (PEG) segments have been evaluated by the single heating methods of Friedman and Freeman-Carroll. The experimental results showed that copolymers exhibited two degradation steps under nitrogen that can be ascribed to PLLA or PDO/PLLA and PEG segments, respectively. However, copolymers exhibited almost single degradation step in air. Although the values of initial decomposition temperature were scattered, copolymers showed the lower maximum weight loss rate and degradation-activation energy in air than in nitrogen whereas the higher value of temperature at the maximum rate of weight loss was observed in air.

• Biomolecules & Therapeutics
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• v.32 no.1
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• pp.65-76
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• 2024

Bortezomib (BTZ) is a proteasome inhibitor used to treat multiple myeloma (MM). However, the induction of peripheral neuropathy is one of the major concerns in using BTZ to treat MM. In the current study, we have explored the effects of BTZ (0.01-5 nM) on rat neural stem cells (NSCs). BTZ (5 nM) induced cell death; however, the percentage of neurons was increased in the presence of mitogens. BTZ reduced the B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein ratio in proliferating NSCs and differentiated cells. Inhibition of βIII-tubulin (TUBB3) degradation was observed, but not inhibition of glial fibrillary acidic protein degradation, and a potential PEST sequence was solely found in TUBB3. In the presence of growth factors, BTZ increased cAMP response element-binding protein (CREB) phosphorylation, brain-derived neurotrophic factor (Bdnf) transcription, BDNF expression, and Tubb3 transcription in NSCs. However, in the neuroblastoma cell line, SH-SY5Y, BTZ (1-20 nM) only increased cell death without increasing CREB phosphorylation, Bdnf transcription, or TUBB3 induction. These results suggest that although BTZ induces cell death, it activates neurogenic signals and induces neurogenesis in NSCs.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.1
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• pp.83-91
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• 2024

Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor activated under hypoxic conditions, and it plays a crucial role in cellular stress regulation. While HIF-1α activity is essential in normal tissues, its presence in the tumor microenvironment represents a significant risk factor as it can induce angiogenesis and confer resistance to anti-cancer drugs, thereby contributing to poor prognoses. Typically, HIF-1α undergoes rapid degradation in normoxic conditions via oxygen-dependent degradation mechanisms. However, certain cancer cells can express HIF-1α even under normoxia. In this study, we observed an inclination toward increased normoxic HIF-1α expression in cancer cell lines exhibiting increased HDAC6 expression, which prompted the hypothesis that HDAC6 may modulate HIF-1α stability in normoxic conditions. To prove this hypothesis, several cancer cells with relatively higher HIF-1α levels under normoxic conditions were treated with ACY-241, a selective HDAC6 inhibitor, and small interfering RNAs for HDAC6 knockdown. Our data revealed a significant reduction in HIF-1α expression upon HDAC6 inhibition. Moreover, the downregulation of HIF-1α under normoxic conditions decreased zinc finger E-box-binding homeobox 1 expression and increased E-cadherin levels in lung cancer H1975 cells, consequently suppressing cell invasion and migration. ACY-241 treatment also demonstrated an inhibitory effect on cell invasion and migration by reducing HIF-1α level. This study confirms that HDAC6 knockdown and ACY-241 treatment effectively decrease HIF-1α expression under normoxia, thereby suppressing the epithelial-mesenchymal transition. These findings highlight the potential of selective HDAC6 inhibition as an innovative therapeutic strategy for lung cancer.

• Journal of Microbiology and Biotechnology
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• v.27 no.12
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• pp.2119-2128
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• 2017

Citrinin (CIT) is a toxic secondary metabolite produced by fungi belonging to the Penicillium, Aspergillus, and Monascus spp. This toxin has been detected in many agricultural products. In this study, a strain Y3 with the ability to eliminate CIT was screened and identified as Cryptococcus podzolicus, based on the sequence analysis of the internal transcribed spacer region. Neither uptake of CIT by cells nor adsorption by cell wall was involved in CIT elimination by Cryptococcus podzolicus Y3. The extracellular metabolites of Cryptococcus podzolicus Y3 stimulated by CIT or not showed no degradation for CIT. It indicated that CIT elimination was attributed to the degradation of intracellular enzyme(s). The degradation of CIT by C. podzolicus Y3 was dependent on the type of media, yeast concentration, temperature, pH, and initial concentration of CIT. Most of the CIT was degraded by C. podzolicus Y3 in NYDB medium at 42 h but not in PDB medium. The degradation rate of CIT was the highest (94%) when the concentration of C. podzolicus Y3 was $1{\times}10^8cells/ml$. The quantity of CIT degradation was highest at $28^{\circ}C$, and there was no degradation observed at 3$5^{\circ}C$. The study also showed that acidic condition (pH 4.0) was the most favorable for CIT degradation by C. podzolicus Y3. The degradation rate of CIT increased to 98% as the concentration of CIT was increased to $20{\mu}g/ml$. The toxicity of CIT degradation product(s) toward HEK293 was much lower than that of CIT.

• Microbiology and Biotechnology Letters
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• v.20 no.4
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• pp.390-394
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• 1992

Some enzymatic characteristics of the aflatoxin degrading factor produced extraceIlularly by Aspergillus awamori var. fumeus were investigated. When aflatoxin B1 was incubated with the culture filtrate of A. awamori var. fumeus. 60% of it was degraded within an hour. The degradation rate decreased with time and there was virtually no degradation after one hour. The apparent Michaelis constant ($K_m$) determined by Lineweaver-Burk plot was $10.2{\mu}M$. The optimum degradation was observed at $30^{\circ}C$ and pH 5. For the degradation, molecular oxygen seemed to be required. The degradation was enhanced by the $Co^{2+}$. but was inhibited by many other ions like $Fe^{2+}$, $Ca^{2+}$. $Mg^{2+}$, $Zn^{2+}$,$Cu^{2+}$, and $Ba^{2+}$, The presence of either KeN or metyrapone inhibited the reaction while that of $NaI0_4$ cytochrome C or NADPH showed no effect.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.34-34
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• 2003

Protein unfolding is a key step in several cellular processes, including protein translocation across some membranes and protein degradation by ATP-dependent proteases. C1pAP protease and the proteasome can actively unfold proteins in a process that hydrolyzes ATP, These proteases catalyze unfolding by processively unraveling their substrates from the attachment point of the degradation signal. As a consequence, the ability of a protein to be degraded depends on its structure as well as its stability. An ${\alpha}$-helix is easier to unravel than a ${\beta}$-strand. In multidomain proteins, independently stable domains are unfolded sequentially. The steric constraints imposed on substrate proteins during their degradation by the proteasome were investigated by constructing a model protein in which specific parts of the polypeptide chain were covalently connected through disulfide bridges. The cross-linked model proteins were fully degraded by the proteasome, but two or more cross-links retarded the degradation slightly. Our results suggest that the pore of the proteasome allows the concurrent passage of at least three stretches of a polypeptide chain, and also explain the limited degradation by the proteasome that occurs in the processing of the transcription factor NF-KB, and also implicate difficulty in degradation of amyloidal aggregates by the proteasome