• Title/Summary/Keyword: shock proteins

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Autophagy in Ischemic Livers: A Critical Role of Sirtuin 1/Mitofusin 2 Axis in Autophagy Induction

  • Chun, Sung Kook;Go, Kristina;Yang, Ming-Jim;Zendejas, Ivan;Behrns, Kevin E.;Kim, Jae-Sung
    • Toxicological Research
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    • v.32 no.1
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    • pp.35-46
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    • 2016
  • No-flow ischemia occurs during cardiac arrest, hemorrhagic shock, liver resection and transplantation. Recovery of blood flow and normal physiological pH, however, irreversibly injures the liver and other tissues. Although the liver has the powerful machinery for mitochondrial quality control, a process called mitophagy, mitochondrial dysfunction and subsequent cell death occur after reperfusion. Growing evidence indicates that reperfusion impairs mitophagy, leading to mitochondrial dysfunction, defective oxidative phosphorylation, accumulation of toxic metabolites, energy loss and ultimately cell death. The importance of acetylation/deacetylation cycle in the mitochondria and mitophagy has recently gained attention. Emerging data suggest that sirtuins, enzymes deacetylating a variety of target proteins in cellular metabolism, survival and longevity, may also act as an autophagy modulator. This review highlights recent advances of our understanding of a mechanistic correlation between sirtuin 1, mitophagy and ischemic liver injury.

Changes of Rice Storage Proteins Affected by Dry and Storage Temperature (건조 및 저장조건에 따른 쌀 저장단백질의 변화양상)

  • Shin, Pyung-Gyun;Chang, An-Cheol;Hong, Seong-Chang;Lee, Ki-Sang;Lee, Keum-Hee;Lee, Yong-Bok
    • Korean Journal of Environmental Agriculture
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    • v.27 no.4
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    • pp.456-459
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    • 2008
  • Quality of rice grain changes during dry storage with internal physiological changes and external injury by organism. Storage rice changes by condition with respiration via variable temperature, hydrolysis enzyme reaction, lipid peroxidation occurs with change of palatability. During dry storage, physiological change with protein variation pattern was examined by image analysis on proteomic technology. Analysis revealed that protein activity had no change store at room temperature and store at $40^{\circ}C$, but decreased store at $60^{\circ}C$. Analysis of variable hydrophobic protein pattern revealed that protein activity of beta-tubulin, protein disulfide isomerase, vacuolar ATPase b subunit, globulin was not significantly decreased all dry and store condition. However, heat shock protein 70, and glutathione transferase was significantly decreased when rice dried at $60^{\circ}C$ compared with room temperature and $40^{\circ}C$ dry condition.

Synthesis of 2',4'-Dimethoxychalcone Derivatives and Evaluation of Their Antitumor Activities Against Non-small Cell Lung Cancer (2',4'-Dimethoxychalcone 유도체 합성 및 비소폐암세포주에서 항암 활성평가)

  • Choi, Myeong A;Jeong, Ju Hui;Oh, Yong Jin;Lee, Young Sook;Seo, Young Ho
    • YAKHAK HOEJI
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    • v.60 no.3
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    • pp.135-140
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    • 2016
  • Heat shock protein 90 (Hsp90) is a ubiquitous molecular chaperone, which is associated with stabilization of many oncogenic proteins for cancer cell survival. Hsp90 is overexpressed 2-10 fold higher in cancer cells than normal cells. Due to its potential to simultaneously disable multiple signaling pathway, Hsp90 has been identified as a validated target for cancer therapy. Accordingly, we designed and synthesized 2',4'-dimethoxychalcone derivatives to inhibit Hsp90 chaperone function. Among 2',4'-dimethoxychalcone derivatives, we found that compound 1g disrupted Hsp90 chaperoning function and impaired the growth of cancer cells. These findings indicated that 1g could serve a potential lead compound to target Hsp90 in cancer chemotherapy.

Anticancer Effects of the Hsp90 Inhibitor 17-Demethoxy-Reblastatin in Human Breast Cancer MDA-MB-231 Cells

  • Zhao, Qing;Wu, Cheng-Zhu;Lee, Jae Kyoung;Zhao, Su-Rong;Li, Hong-Mei;Huo, Qiang;Ma, Tao;Zhang, Jin;Hong, Young-Soo;Liu, Hao
    • Journal of Microbiology and Biotechnology
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    • v.24 no.7
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    • pp.914-920
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    • 2014
  • Triple-negative breast cancer (TNBC) possesses a higher rate of distant recurrence and a poorer prognosis than other breast cancer subtypes. Interestingly, most of the heat shock protein 90 (Hsp90) client proteins are oncoproteins, and some are closely related to unfavorable factors of TNBC patients. 17-Demethoxy-reblastatin (17-DR), a novel non-benzoquinone-type geldanamycin analog, exhibited potent Hsp90 ATPase inhibition activity. In this study, the anticancer effects of 17-DR on TNBC MDA-MB-231 cells were investigated. These results showed that 17-DR inhibited cell proliferation, induced apoptosis, and suppressed cell invasion and migration in the MDA-MB-231 cells. Down-regulation of the key Hsp90-dependent tumor-driving molecules, such as RIP1 and MMP-9, by 17-DR may be related to these effects. Taken together, our results suggest that 17-DR has potential as a therapeutic agent for the treatment of TNBC.

A chaperone surveillance system in plant circadian rhythms

  • Cha, Joon-Yung;Khaleda, Laila;Park, Hee Jin;Kim, Woe-Yeon
    • BMB Reports
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    • v.50 no.5
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    • pp.235-236
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    • 2017
  • The circadian clock is an internal system that is synchronized by external stimuli, such as light and temperature, and influences various physiological and developmental processes in living organisms. In the model plant Arabidopsis, transcriptional, translational and post-translational processes are interlocked by feedback loops among morning- and evening-phased genes. In a post-translational loop, plant-specific single-gene encoded GIGANTEA (GI) stabilize the F-box protein ZEITLUPE (ZTL), driving the targeted-proteasomal degradation of TIMING OF CAB EXPRESSION 1 (TOC1) and PSEUDO-RESPONSE REGULATOR 5 (PRR5). Inherent to this, we demonstrate the novel biochemical function of GI as a chaperone and/or co-chaperone of Heat-Shock Protein 90 (HSP90). GI prevents ZTL degradation as a chaperone and facilitates ZTL maturation together with HSP90/HSP70, enhancing ZTL activity in vitro and in planta. GI is known to be involved in a wide range of physiology and development as well as abiotic stress responses in plants, but it could also interact with diverse client proteins to increase protein maturation. Our results provide evidence that GI helps proteostasis of ZTL by acting as a chaperone and a co-chaperone of HSP90 for proper functioning of the Arabidopsis circadian clock.

Immunogenicity and Protective Efficacy of an Oral Vaccine against Vibrio vulnificus Infection (경구투여한 V. vulnificus 백신의 면역원성 및 감염방어효능)

  • 이나경;정상보;안보영;김영지;이윤하
    • Biomolecules & Therapeutics
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    • v.6 no.2
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    • pp.191-198
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    • 1998
  • Vsrio vulnificus is an estuarine gram-negative human pathogen that affects people with chronic hepatitis, alcoholic cirrhosis, diabetes mellitus or other underlying diseases. V. vulnificus infection is mediated primarily by consumption of raw fish or by exposure of pre-existing wounds to seawater, causing permanent tissue damages or fatal septic shock. We have been developing a vaccine against V. vulnificus composed of whole cell Iysate of a V. vulnificus O-antigen serotype 4 strain. Oral administration of the V. vulnificus;oral vaccine;immunogenicity;protective efficacy vaccine elicited a high serum antibody response in rabbits. The induced antibodies were reactive not only to the homologous strain but also to heterologous O-antigen serotype strains, indicating cross-reactivities among serotypes. Western blot analysis revealed that the antibodies are mainly specific for outer membrane proteins (OMPs) and reacted equally well with OMPs purified from 9 O-antigen serotypes. The rabbit antisera showed opsonophagocytic killing activity against heterologous strains as well as the homologous strain. Passively transferred rabbit antisera into mice were protective against a lethal V. vulnificus infection. These data demonstrate that oral administration of the V. vulnificus vaccine induced a systemic antibody response which had a protective efficacy against V. vulnificus infections, suggesting that this vaccine preparation could be used to develop an oral vaccine against V. vulnificus.

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Antigenicity of DA-3002, a Genuine Recombinant Human growth Hormone, in Guinea Pigs and Mice (천연형 인성장호르몬 DA-3002의 항원성)

  • 강경구;백남기;김원배;양중익
    • Biomolecules & Therapeutics
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    • v.3 no.4
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    • pp.251-255
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    • 1995
  • DA-3002 is a genuine human growth hormone produced by Dong-A Pharm. Co. Ltd. research laboratory using recombinant DNA technic. In this study, antigenic potential of DA-3002 was examined by active systemic anaphyaxis(ASA) in guinea pigs, mouse-rat passive cutaneous anaphylaxis(PCA) and passive hemagglutination(PHA) test as a part of safety research. DA-3002 induced anaphylactic shock in ASA test using guinea pigs Immunized with DA-3002 alone or DA-3002 incoporated into Freund's complete adjutant(FCA) when challenged with 10 times higher dose of anticipated clinical dose of DA-3002. In the mouse-rat PCA and PHA test, DA-3002 also showed positive results. DA-3002, therfore, was considered to produce IgE, IgG, and/or IgM in mice. The results of this study were similar to those of the other human growth hormones and these positive results were thought to be caused due to the fact that both DA-3002 and the other human growth hormones were heterogenous proteins to guinea pigs and mice. Considering the fact that DA-3002 is a genuine human growth hormone of which structure is identical with indigenous human growth hormone, DA-3002 is thought not to cause immunological problems in clinical use.

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Polygonatum sibiricum component liquiritigenin restrains breast cancer cell invasion and migration by inhibiting HSP90 and chaperone-mediated autophagy

  • Suli Xu;Zhao Ma;Lihua Xing;Weiqing Cheng
    • The Korean Journal of Physiology and Pharmacology
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    • v.28 no.4
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    • pp.379-387
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    • 2024
  • Breast cancer (BC) is most commonly diagnosed worldwide. Liquiritigenin is a flavonoid found in various species of the Glycyrrhiza genus, showing anti-tumor activity. This article was to explore the influences of liquiritigenin on the biological behaviors of BC cells and its underlying mechanism. BC cells were treated with liquiritigenin alone or transfected with oe-HSP90 before liquiritigenin treatment. RT-qPCR and Western blotting were employed to examine the levels of HSP90, Snail, E-cadherin, HSC70, and LAMP-2A. Cell viability, proliferation, migration, and invasion were evaluated by performing MTT, colony formation, scratch, and Transwell assays, respectively. Liquiritigenin treatment reduced HSP90 and Snail levels and enhanced E-cadherin expression as well as inhibiting the proliferation, migration, and invasion of BC cells. Moreover, liquiritigenin treatment decreased the expression of HSC70 and LAMP-2A, proteins related to chaperone-mediated autophagy (CMA). HSP90 overexpression promoted the CMA, invasion, and migration of BC cells under liquiritigenin treatment. Liquiritigenin inhibits HSP90-mediated CMA, thereby suppressing BC cell growth.

The Effect of Exercise Training (EXE) on Myocardium Glucose Metabolic Phenotypic Proteins and HSP-60 Protein Expression after Ischemia/Reperfusion Injury in STZ-induced Rats (지구성 운동이 STZ-당뇨 유발 쥐의 허혈/재 관류 손상 후 심근의 당대사 관련 표현형 단백질과 HSP-60 단백질 발현에 미치는 영향)

  • Bae, Hee-Suk;Um, Hyun-Seob;Kang, Eun-Bum;Yang, Chum-Yeol;Lee, Yong-Ro;Lee, Chang-Guk;Cheon, U-Ho;Jeon, Hye-Ja;Cho, In-Ho;Cho, Joon-Yong
    • Journal of Life Science
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    • v.19 no.5
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    • pp.644-651
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    • 2009
  • The objective of this study was to identify EXE (1 hr a day at 21 m/min for 5 day/wk, at 0 % grade for 6 wk) on myocardium glucose metabolic phenotypic proteins (AMPK-PGC-1${\alpha}$-GLUT-4) and HSP-60 protein expression after ischemia/reperfusion injury (IRI) in STZ-induced rats. EXE was performed using STZ-induced diabetic rats on a rodent treadmill (28 m/min, 1 hr/day, 5 day/wk for 6 wk). The results of this study suggest that i) serum insulin level was not changed among groups (p>l0.05). ii) the LVDP level increased significantly in the STZ-EXE-IRI group compared to the STZ-IRI group at 60 min (p<0.01), 70 min (p<0.05) and 80 min (p<0.05) after reperfusion, respectively, and iii) AMPK phosphorylation (p<0.01), PGC-1${\alpha}$ protein (p<0.001), GLUT-4 protein (p<0.001) and HSP-60 protein expressions (p<0.05) increased significantly in the STZ-EXE-IRI group compared to the STZ-IRI group. In conclusion, the findings of the present study reveal that EXE may provide therapeutic value to insulin dependent diabetic patients with peripheral insulin resistance and myocardium injury by improving glucose metabolic proteins (AMPK-PGC-1${\alpha}$-GLUT-4) and heat shock protein-60 (HSP-60), along with increasing LVDP levels and decreasing glucose levels. Therefore, EXE protects the STZ-induced diabetic myocardium injury against ischemia/ reperfusion injury.

Aluminum toxicity-induced alterations of root proteome in wheat seedlings

  • Oh, Myeong Won;Roy, Swapan Kumar;Cho, Kun;Cho, Seong-Woo;Park, Chul-Soo;Chung, Keun-Yook;Choi, Jong-Soon;Woo, Sun-Hee
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2017.06a
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    • pp.127-127
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    • 2017
  • Aluminum is the most abundant metallic element in the Earth's crust and considered as the most limiting factor for plant productivity in acidic soils. The inhibition of root growth is recognized as the primary effect of Al toxicity. Seeds of wheat cv. Keumkang (Korean cultivar) were germinated on petridish for 5 days and then transferred hydroponic apparatus which was treated with $0{\mu}M$ $AlCl_3$ (control), $100{\mu}M$ $AlCl_3$ and $150{\mu}M$ $AlCl_3$ for 5 days. The length of roots, shoots and fresh weight of wheat seedlings were decreased under aluminum stress. The concentrations of $K^+$, $Mg^{2+}$ and $Ac^{2+}$ were decreased whereas $Al^{3+}$ and $P_2O_5{^-}$ concentration was increased under aluminum stress. Using confocal microscopy, the fluorescence intensity of aluminum was increased with morin staining. In this study, a proteome analysis was performed to identify proteins, which is responsible to aluminum stress in wheat roots. In 10-day-old seedlings, proteins were extracted from roots and separated by 2-DE, stained by CBB. Using image analysis, a total of 47 differentially expressed protein spots were selected, whereas 19 protein spots were significantly up-regulated such as s-adenosylmethionine, oxalate oxidase, malate dehydrogenase, cysteine synthase, ascorbate peroxidase and 28 protein spots were significantly down-regulated such as heat shock protein 70, o-methytransferase 4, enolase, amylogenin by aluminum stress following protein spots analyzed by LTQ-FTICR mass spectrometry. The results provide the global picture of Al toxicity-induced alterations of protein profiles in wheat roots, and identify the Al toxicity-responsive proteins related to various biological processes that may provide some novel clues about plant Al tolerance.

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