• Biomolecules & Therapeutics
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• 제32권1호
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• pp.115-122
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• 2024

Heat shock protein (HSP) 90 is expressed in most living organisms, and several client proteins of HSP90 are necessary for cancer cell survival and growth. Previously, we found that HSP90 was cleaved by histone deacetylase (HDAC) inhibitors and proteasome inhibitors, and the cleavage of HSP90 contributes to their cytotoxicity in K562 leukemia cells. In this study, we first established mouse xenograft models with K562 cells expressing the wild-type or cleavage-resistant mutant HSP90β and found that the suppression of tumor growth by the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) was interrupted by the mutation inhibiting the HSP90 cleavage in vivo. Next, we investigated the possible function of thioredoxin interacting protein (TXNIP) in the HSP90 cleavage induced by SAHA. TXNIP is a negative regulator for thioredoxin, an antioxidant protein. SAHA transcriptionally induced the expression of TXNIP in K562 cells. HSP90 cleavage was induced by SAHA also in the thymocytes of normal mice and suppressed by an anti-oxidant and pan-caspase inhibitor. When the thymocytes from the TXNIP knockout mice and their wild-type littermate control mice were treated with SAHA, the HSP90 cleavage was detected in the thymocytes of the littermate controls but suppressed in those of the TXNIP knockout mice suggesting the requirement of TXNIP for HSP90 cleavage. We additionally found that HSP90 cleavage was induced by actinomycin D, β-mercaptoethanol, and p38 MAPK inhibitor PD169316 suggesting its prevalence. Taken together, we suggest that HSP90 cleavage occurs also in vivo and contributes to the anti-cancer activity of various drugs in a TXNIP-dependent manner.

• 한국수정란이식학회지
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• 제9권3호
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• pp.269-277
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• 1994

The objective of this study was to develop an effective in vitro production system capable of obtaining more porcine embryos from immature oocytes These experiments were conducted to examine the effect of sperm factor on the IVF and IVD, and the effect of coculture with somatic cells on the IVD of embryos. Although the concentration of epididymal sperm for IVF did not affect on cleavage rate, but 5 x 105 sperm/mi showed the highest cleavage rate(48.7%) and the developmental potential of IVF oocytes from this concentration was also greatly higher (P$^{\circ}C$-stored sperm for l2hrs and the cleavage rate from fresh sperm was significantly higher (P<0.05) than that from frozen sperm, but the developmental potential after IVF was slightly high from the frozen sperm. The cleavage rate of IVF oocytes cocultured with oviductal epithelial cells and cumulus cells was 76.3% and 72.9%, respectively. There was no difference between two coculture systems but this rate was significantly higher(P<0.05) than that of medium alone(42.0%).

• 미생물학회지
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• 제38권4호
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• pp.245-245
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• 2002

Catabolic pathways for the degradation of various aromatics by Sphingomonas yanoikuyae Bl are intertwined, joining at the level of substituted benzoates, which are further degraded vita ring cleavage reactions. The mutant strain EK497, which was constructed by deleting a large DNA region containing most of the genes for biphenyl, naphthalene, m-xylene, and m-toluate degradation, was unable to grow on all of the aromatics tested except for benzoate as the sole source of carbon and energy.S. yanoikuyae EK497 was found to possess only catechol ortho-ring cleavage activity due to deletion of the genes for the meta-cleavage pathway. Wild-type S. yanoikuyae Bl grown on benzoate has both catechol orthoand meta-cleavage activity. However, m-xylene and m-toluate, which are metabolized through methylbenzoate, and biphenyl, which is metabolized through benzoate, induce only the meta-cleavage pathway, suggesting the presence of a substrate-dependent induction mechanism.

• Bulletin of the Korean Chemical Society
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• 제28권12호
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• pp.2329-2332
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• 2007

Salsolinol, endogenous neurotoxin, is known to be involved in the pathogenesis of Parkinson's disease (PD). In the present study, we have investigated the oxidative damage of DNA induced by the reaction of salsolinol with Cu,Zn-SOD. When plasmid DNA incubated with salsolinol and Cu,Zn-SOD, DNA cleavage was proportional to the concentrations of salsolinol and Cu,Zn-SOD. The salsolinol/Cu,Zn-SOD system-mediated DNA cleavage was significantly inhibited by radical scavengers such as mannitol, ethanol and thiourea. These results indicated that free radicals might participate in DNA cleavage by the salsolinol/Cu,Zn-SOD system. Spectrophotometric study using a thiobarbituric acid showed that hydroxyl radical formation was proportional to the concentration of salsolinol and was inhibited by radical scavengers. These results indicated that hydroxyl radical generated in the reaction of salsolinol with Cu,Zn-SOD was implicated in the DNA cleavage. Catalase and copper chelators inhibited DNA cleavage and the production of hydroxyl radicals. These results suggest that DNA cleavage is mediated in the reaction of salsolinol with Cu,Zn-SOD via the generation of hydroxyl radical by a combination of the oxidation reaction of salsolinol and Fenton-like reaction of free copper ions released from oxidatively damaged SOD.

• Biomolecules & Therapeutics
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• 제27권5호
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• pp.423-434
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• 2019

HSP90 is a molecular chaperone that increases the stability of client proteins. Cancer cells show higher HSP90 expression than normal cells because many client proteins play an important role in the growth and survival of cancer cells. HSP90 inhibitors mainly bind to the ATP binding site of HSP90 and inhibit HSP90 activity, and these inhibitors can be distinguished as ansamycin and non-ansamycin depending on the structure. In addition, the histone deacetylase inhibitors inhibit the activity of HSP90 through acetylation of HSP90. These HSP90 inhibitors have undergone or are undergoing clinical trials for the treatment of cancer. On the other hand, recent studies have reported that various reagents induce cleavage of HSP90, resulting in reduced HSP90 client proteins and growth suppression in cancer cells. Cleavage of HSP90 can be divided into enzymatic cleavage and non-enzymatic cleavage. Therefore, reagents inducing cleavage of HSP90 can be classified as another class of HSP90 inhibitors. We discuss that the cleavage of HSP90 can be another mechanism in the cancer treatment by HSP90 inhibition.

• Applied Microscopy
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• 제34권1호
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• pp.71-81
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• 2004

본 연구에서는 등황란인 U. unicinctus 수정란의 난할과정과 형식에 대하여 관찰된 바를 보고하였다. U unicinctus성숙란을 인공수정했을 때 난할은 핵 개방(germinal vesicle breakdown)과 제1, 2감수분열 후에 수행되었으며, 유생기 까지 난할은 등할(equal cleavage), 전할(holoblastic cleavage)이었고 난할형식은 나선형 난할(spiral cleavage)인 것으로 관찰되었다. 최초 3회의 난할이 경할$\rightarrow$경할$\rightarrow$수평할이었고, 이후 경할-수평할이 반복되는 것으로 보였다. 4세포기에 할구의 배열에서 일부 할구들이 동물극으로 융기한 것과 8세포기에서 식물극 할구 배열이 동물극 할구 배열에 대하여 사선 배열한 것 등은 나선형 난할에서만 볼 수 있는 특징이었으나 제 3차 난할인 수평할에서 등할, 전할인 것이 관찰되므로서 나선형 난할을 수행하는 Spiralian의 전형에 속하지는 않는 것으로 보였다. 4세포기 이후의 할구 배열이 사선배열, 즉 나선형인 근거를 항-$\alpha$-,-$\beta$-튜블린 처리에 의해 관찰된 유사분열 기구의 행위로서 볼 수 있었다. 4$\rightarrow$8세포기의 유사분열 기구는 동물극-식물극 축에 수직으로 발생하고 사선방향으로 선회한 후 난할하므로서 결과에서 수평할 및 할구의 사선배열이 가능한 것을 볼 수 있었다.

• 열처리공학회지
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• 제27권3호
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• pp.133-140
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• 2014

Cleavage fracture behaviors were investigated in Ni-Mo-Cr steels with mixed microstructure of lower bainite and martensite. As the size of carbide decreased, the cleavage fracture strength increased, which was independent of the sizes of grain and packet. The measured cleavage fracture strengths were in good agreement with cleavage fracture strengths calculated by Petch model rather than by modified Griffith model in micro-structures with fine carbides, the size of which were small below a few hundred nanometer.

• BMB Reports
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• 제51권5호
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• pp.211-218
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• 2018

Chromatin is an intelligent building block that can express either external or internal needs through structural changes. To date, three methods to change chromatin structure and regulate gene expression have been well-documented: histone modification, histone exchange, and ATP-dependent chromatin remodeling. Recently, a growing body of literature has suggested that histone tail cleavage is related to various cellular processes including stem cell differentiation, osteoclast differentiation, granulocyte differentiation, mammary gland differentiation, viral infection, aging, and yeast sporulation. Although the underlying mechanisms suggesting how histone cleavage affects gene expression in view of chromatin structure are only beginning to be understood, it is clear that this process is a novel transcriptional epigenetic mechanism involving chromatin dynamics. In this review, we describe the functional properties of the known histone tail cleavage with its proteolytic enzymes, discuss how histone cleavage impacts gene expression, and present future directions for this area of study.

• Bulletin of the Korean Chemical Society
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• 제26권12호
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• pp.2033-2037
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• 2005

In vitro selection was used to isolate $Mg^{2+}$-dependent self-cleaving ribozymes with cis-cleavage activity from a pre-tRNA library having 40-mer random sequences attached to 5'-end of E. coli $tRNA^{Phe}$. After 8 rounds of SELEX (Systematic Evolution of Ligands by Exponential Enrichment), RNA molecules which can self-cleave at the high concentration of $Mg^{2+}$ were isolated. The selected ribozymes can carry out the self-cleavage reaction in the presence of 100 mM $Mg^{2+}$ but not in 10 mM $Mg^{2+}$. The cleavage sites of the ribozymes are located at +3 and +4 of $tRNA^{Phe}$, compared with +1 position of 5'-end cleavage site of pre-tRNA by RNase P. New RNA constructs deprived of its D stem-loop, anticodon stem-loop, variable loop and T stem-loop, respectively showed the cleavage specificity identical to a ribozyme having the intact tRNA structure. Also, the new ribozyme fused with both a ribozyme and $tRNA^{Leu}$ showed the cleavage activities at the various sites within its sequences, different from two sites of position +3 and +4 observed in the ribozyme with $tRNA^{Phe}$. Our results suggest that the selected ribozyme is not structural-specific for tRNA.

• Bulletin of the Korean Chemical Society
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• 제26권8호
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• pp.1251-1254
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• 2005

It has been proposed that oxidation of L-3,4-dihydroxyphenylalanine (DOPA) may contribute to the pathogenesis of neurodegenerative disease. In this study, L-DOPA-Fe(III)-mediated DNA cleavage and the protection by carnosine and homocarnosine against this reaction were investigated. When plasmid DNA was incubated with L-DOPA in the presence of Fe(III), DNA strand was cleaved. Radical scavengers and catalase significantly inhibited the DNA breakage. These results suggest that $H_2O_2$ may be generated from the oxidation of DOPA and then $Fe^{3+}$ likely participates in a Fenton’s type reaction to produce hydroxyl radicals, which may cause DNA cleavage. Carnosine and homocarnosine have been proposed to act as anti-oxidants in vivo. The protective effects of carnosine and homocarnosine against L-DOPA-Fe(III)-mediated DNA cleavage have been studied. Carnosine and homocarnosine significantly inhibited DNA cleavage. These compounds also inhibited the production of hydroxyl radicals in L-DOPA/$Fe^{3+}$ system. The results suggest that carnosine and homocarnosine act as hydroxyl radical scavenger to protect DNA cleavage. It is proposed that carnosine and homocarnosine might be explored as potential therapeutic agents for pathologies that involve damage of DNA by oxidation of DOPA.