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Sangkyu Park Jeong-A Park Young-Eun Kim Sukgil Song Hyung-Joo Kwon Younghee Lee 《Cell stress & chaperones》2015,20(1):149-157
Heat shock protein 90 (HSP90) is a molecular chaperone that supports stability of client proteins. We found that HSP90 was cleaved to 55 kDa protein after treatment with histone deacetylase (HDAC) inhibitors including suberoylanilide hydroxamic acid (SAHA) in several leukemia cell lines. We further analyzed molecular changes induced by SAHA in K562 cells. The SAHA-induced cleavage of HSP90 was blocked by a pan-caspase inhibitor, z-VAD-fmk, implying that the process is dependent on caspase activity. However, the experiments using antagonistic and agonistic Fas antibodies revealed that the cleavage of HSP90 was not dependent on Fas signaling. SAHA induced generation of reactive oxygen species (ROS), and the cleavage of HSP90 was blocked by a ROS scavenger N-acetylcystein (NAC). We also confirmed that hydrogen peroxide (H2O2) induced cleavage of HSP90 in a similar manner. Caspase 2, 3, 4, 6, 8, and 10 were activated by treatment with SAHA, and the activities were reduced by the pretreatment of NAC. Treatment of the cells with caspase 10 inhihitor, but not other inhibitors of caspases activated by SAHA, prevented cleavage of HSP90 by SAHA. SAHA-induced ROS generation and HSP90 cleavage were dependent on newly synthesized unknown proteins. Taken together, our results suggest that the cleavage of HSP90 by SAHA is mediated by ROS generation and caspase 10 activation. HSP90 cleavage may provide an additional mechanism involved in anti-cancer effects of HDAC inhibitors.
Electronic supplementary material
The online version of this article (doi:10.1007/s12192-014-0533-4) contains supplementary material, which is available to authorized users. 相似文献22.
Ha Lim Oh Haeyoung Lim Younghee Park Yoongho Lim Hyun Chul Koh Youl-Hee Cho Chul-Hoon Lee 《Bioorganic & medicinal chemistry letters》2009,19(3):797-799
This study was aimed to elucidate the novel structure of HY253 isolated from the roots of Aralia continentalis and to evaluate its detailed mechanisms on apoptotic induction in HY253-treated HeLa cells. The structure of HY253 was elucidated based on the interpretation of the NMR spectra, as 7,8a-divinyl-2,4a,4b,5,6,7,8,8a,9,9a-decahydro-1H-fluorene-2,4a,4b,9a-tetraol. The TUNEL assay using flow cytometer revealed an appreciable apoptotic induction in HeLa cells treated with 100 μM of HY253 for 48 h. This apoptotic induction is associated with cytochrome c release from mitochondria, via up-regulation of pro-apoptotic Bcl-2 proteins, such as Bax and Bak, which, in turn, resulted in the activation of caspase-8, -9 and -3, and the cleavage of poly(ADP-ribose) polymerase (PARP). 相似文献
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Glycosylation is the most important and abundant post-translational modification in serum proteome. Several specific types
of glycan epitopes have been shown to be associated with various types of disease. Direct analysis of serum glycoproteins
is challenging due to its wide dynamic range. Alternatively, glycoproteins can be discovered in the secretome of model cell
lines and then confirmed in blood. However, there has been little experi-mental evidence showing cell line secretome as a
tractable target for the study of serum glycoproteins. We used a hydrazine-based glycocapture method to selectively enrich
glycoproteins from the secretome of the breast cancer cell line Hs578T. A total of 132 glycoproteins were identified by nanoLC-MS/MS
analysis. Among the identified proteins, we selected 13 proteins that had one or more N-glycosylation motifs in the matched peptides, which were included in the Secreted Protein Database but not yet in the Plasma
Proteome Database (PPD), and whose antibodies were commercially available. Nine out of the 13 selected proteins were detected
from human blood plasma by western analysis. Furthermore, eight proteins were also detected from the plasma by targeted LC-MS/MS,
which had never been previously identified by data-dependent LC-MS/MS. Our results provide novel proteins that should be enrolled
in PPD and suggest that analysis of cell line secretome with subfractionation is an efficient strategy for discovering disease-relevant
serum proteins. 相似文献
24.
Jian-Min Zhou Eunjung Lee Francesca Kanapathy-Sinnaiaha Younghee Park Jack A Kornblatt Yoongho Lim Ragai K Ibrahim 《BMC plant biology》2010,10(1):156
Background
Wheat (Triticum aestivum L.) O-methyltransferase (TaOMT2) catalyzes the sequential methylation of the flavone, tricetin, to its 3'-methyl- (selgin), 3',5'-dimethyl- (tricin) and 3',4',5'-trimethyl ether derivatives. Tricin, a potential multifunctional nutraceutical, is the major enzyme reaction product. These successive methylations raised the question as to whether they take place in one, or different active sites. We constructed a 3-D model of this protein using the crystal structure of the highly homologous Medicago sativa caffeic acid/5-hydroxyferulic acid O-methyltransferase (MsCOMT) as a template with the aim of proposing a mechanism for multiple methyl transfer reactions in wheat. 相似文献25.
Hydrogen sulfide degradation characteristics of Bordetella sp. Sulf-8 in a biotrickling filter 总被引:1,自引:0,他引:1
Grace M. Nisola Enkhdul Tuuguu Danvir Mark D. Farnazo Mideok Han Younghee Kim Eulsaeng Cho Wook-Jin Chung 《Bioprocess and biosystems engineering》2010,33(9):1131-1138
The applicability of Bordetella sp. Sulf-8 to degrade Hydrogen Sulfide (H2S) gas in a biotrickling system was investigated. The isolate is a heterotrophic gram-negative, catalase- and oxidase-positive,
rod-shaped bacterium which can metabolize thiosulfate or sulfide into sulfate. The mesophilic Bordetella sp. Sulf-8 can grow within a wide pH range using yeast as carbon source, with or without the presence of sulfur. In batch
experiments, kinetic constants such as maximum specific growth rate (μ
max = 0.12 1/h), saturation constant (K
S = 0.017 g/L), and specific sulfur removal rate (88 mg S/g cells h) were obtained. In biotrickling experiments removal efficiencies
were satisfactory, but the system performance was observed to be more influenced by empty bed residence time than by H2S feed gas concentration. Critical and maximum elimination capacities were 78.0 and 94.5 g H2S/m3 day, respectively. Macrokinetic analysis of the biotrickling system revealed maximum H2S removal rate V
max = 15.97 g S/kg media-day and half saturation constant K
S′ = 12.45 ppmv. 相似文献
26.
Kwon HJ Breese EH Vig-Varga E Luo Y Lee Y Goebl MG Harrington MA 《Molecular and cellular biology》2004,24(21):9317-9326
A myriad of stimuli including proinflammatory cytokines, viruses, and chemical and mechanical insults activate a kinase complex composed of IkappaB kinase beta (IKK-beta), IKK-alpha, and IKK-gamma/N, leading to changes in NF-kappaB-dependent gene expression. However, it is not clear how the NF-kappaB response is tailored to specific cellular insults. Signaling molecule that interacts with mouse pelle-like kinase (SIMPL) is a signaling component required for tumor necrosis factor alpha (TNF-alpha)-dependent but not interleukin-1-dependent NF-kappaB activation. Herein we demonstrate that nuclear localization of SIMPL is required for type I TNF receptor-induced NF-kappaB activity. SIMPL interacts with nuclear p65 in a TNF-alpha-dependent manner to promote endogenous NF-kappaB-dependent gene expression. The interaction between SIMPL and p65 enhances p65 transactivation activity. These data support a model in which TNF-alpha activation of NF-kappaB dependent-gene expression requires nuclear relocalization of p65 as well as nuclear relocalization of SIMPL, generating a TNF-alpha-specific induction of gene expression. 相似文献
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Choi K Yi Y Lee S Kang K Lee E Hong S Young J Park Y Choi GJ Kim BJ Lim Y 《Journal of microbiology and biotechnology》2007,17(5):873-877
In order to find microorganisms showing antifungal activities against Plasmodiophora brassicae, which causes club root, Korean salt-fermented fishery products were tested. Several fermented broths of microorgansims isolated from Ammodytes personatus fishery products showed high antifungal activities. The identification of microorganisms and their in vivo antifungal activities are reported herein. 相似文献
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