• Title/Summary/Keyword: PAO

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Phenylarsine Oxide and Adenosine-sensitive Trans-golgi Complex Targeting of GFP Fused to Modified Sulfatide-binding Peptide (Phenylarsine oxide와 adenosine에 민감한 sulfatide 결합 펩타이드의 trans-golgi network 타기팅)

  • Jun, Yong-Woo;Lee, Jin-A;Jang, Deok-Jin
    • Journal of Life Science
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    • v.28 no.2
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    • pp.162-169
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    • 2018
  • Many cytoplasmic proteins are targeted to the cytoplasmic membrane of the trans-Golgi network (TGN) via an N-terminal short helix. We previously showed that the 20 N-terminal amino acids of Aplysia phosphodiesterase 4 (ApPDE4) long form are sufficient for its targeting to the plasma membrane and the TGN. The N-terminus of the ApPDE4 long form binds to PI4P and sulfatide in vitro. Therefore, in order to decipher the roles of sulfatide in Golgi complex targeting, we examined the cellular localization of sulfatide-binding peptides. In this study, we found that enhanced green fluorescent protein (EGFP) fused to the C-terminus of modified sulfatide- and heparin-binding peptides (mHSBP-EGFP) was localized to the TGN. On the other hand, its mutant, in which tryptophan was replaced with an alanine, leading to the impairment of heparin and sulfatide binding, was localized to cytosol. We also found that the TGN targeting of mHSBP-EGFP is impaired by the treatment of antimycin A, phenylarsine oxide (PAO), and adenosine but not a high concentration of wortmannin. These results suggest that PAO and adenosine-sensitive kinases, including phosphatidylinositol 4-kinase II, may play key roles in the recruitment of mHSBP-EGFP.

Protein phosphorylation on tyrosine restores expression and glycosylation of cyclooxygenase-2 by 2-deoxy-D-glucose-caused endoplasmic reticulum stress in rabbit articular chondrocyte

  • Yu, Seon-Mi;Kim, Song-Ja
    • BMB Reports
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    • v.45 no.5
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    • pp.317-322
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    • 2012
  • 2-deoxy-D-glucose(2DG)-caused endoplasmic reticulum (ER) stress inhibits protein phosphorylation at tyrosine residues. However, the accurate regulatory mechanisms, which determine the inflammatory response of chondrocytes to ER stress via protein tyrosine phosphorylation, have not been systematically evaluated. Thus, in this study, we examined whether protein phosphorylation at tyrosine residues can modulate the expression and glycosylation of COX-2, which is reduced by 2DG-induced ER stress. We observed that protein tyrosine phosphatase (PTP) inhibitors, sodium orthovanadate (SOV), and phenylarsine oxide (PAO) significantly decreased expression of ER stress inducible proteins, glucose-regulated protein 94 (GRP94), and CCAAT/ enhancer-binding-protein- related gene (GADD153), which was induced by 2DG. In addition, we demonstrated that SOV and PAO noticeably restored the expression and glycosylation of COX-2 after treatment with 2DG. These results suggest that protein phosphorylation of tyrosine residues plays an important role in the regulation of expression and glycosylation during 2DG-induced ER stress in rabbit articular chondrocytes.

Polyamines and Their Metabolites as Diagnostic Markers of Human Diseases

  • Park, Myung Hee;Igarashi, Kazuei
    • Biomolecules & Therapeutics
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    • v.21 no.1
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    • pp.1-9
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    • 2013
  • Polyamines, putrescine, spermidine and spermine, are ubiquitous in living cells and are essential for eukaryotic cell growth. These polycations interact with negatively charged molecules such as DNA, RNA, acidic proteins and phospholipids and modulate various cellular functions including macromolecular synthesis. Dysregulation of the polyamine pathway leads to pathological conditions including cancer, inflammation, stroke, renal failure and diabetes. Increase in polyamines and polyamine synthesis enzymes is often associated with tumor growth, and urinary and plasma contents of polyamines and their metabolites have been investigated as diagnostic markers for cancers. Of these, diacetylated derivatives of spermidine and spermine are elevated in the urine of cancer patients and present potential markers for early detection. Enhanced catabolism of cellular polyamines by polyamine oxidases (PAO), spermine oxidase (SMO) or acetylpolyamine oxidase (AcPAO), increases cellular oxidative stress and generates hydrogen peroxide and a reactive toxic metabolite, acrolein, which covalently incorporates into lysine residues of cellular proteins. Levels of protein-conjuagated acrolein (PC-Acro) and polyamine oxidizing enzymes were increased in the locus of brain infarction and in plasma in a mouse model of stroke and also in the plasma of stroke patients. When the combined measurements of PC-Acro, interleukin 6 (IL-6), and C-reactive protein (CRP) were evaluated, even silent brain infarction (SBI) was detected with high sensitivity and specificity. Considering that there are no reliable biochemical markers for early stage of stroke, PC-Acro and PAOs present promising markers. Thus the polyamine metabolites in plasma or urine provide useful tools in early diagnosis of cancer and stroke.

Effects of various prophylactic procedures on titanium surfaces and biofilm formation

  • Di Salle, Anna;Spagnuolo, Gianrico;Conte, Raffaele;Procino, Alfredo;Peluso, Gianfranco;Rengo, Carlo
    • Journal of Periodontal and Implant Science
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    • v.48 no.6
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    • pp.373-382
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    • 2018
  • Purpose: The aim of this study was to evaluate the effects of various prophylactic treatments of titanium implants on bacterial biofilm formation, correlating surface modifications with the biofilms produced by Pseudomonas aeruginosa PAO1, Staphylococcus aureus, and bacteria isolated from saliva. Methods: Pure titanium disks were treated with various prophylactic procedures, and atomic force microscopy (AFM) was used to determine the degree to which surface roughness was modified. To evaluate antibiofilm activity, we used P. aeruginosa PAO1, S. aureus, and saliva-isolated Streptococcus spp., Bacteroides fragilis, and Staphylococcus epidermidis. Results: AFM showed that the surface roughness increased after using the air-polishing device and ultrasonic scaler, while a significant reduction was observed after using a curette or polishing with Detartrine ZTM (DZ) abrasive paste. In addition, we only observed a significant (P<0.01) reduction in biofilm formation on the DZ-treated implant surfaces. Conclusion: In this study, both AFM and antibiofilm analyses indicated that using DZ abrasive paste could be considered as the prophylactic procedure of choice for managing peri-implant lesions and for therapy-resistant cases of periodontitis.

A Study on Improvement of Test Method of Nuclear Power Plant ESF ACS by applying Regulatory Guide 1.52 (Rev.3) (Reg. Guide 1.52(Rev.3)를 적용한 원전 ESF 공기정화계통 성능시험법 개선 연구)

  • Lee, Sook-Kyung;Kim, Kwang-Sin;Sohn, Soon-Hwan;Song, Kyu-Min;Lee, Kae-Woo;Park, Jeong-Seo;Cho, Byoung-Ho;Yoo, Byeang-Jea;Hong, Soon-Joon;Kang, Sun-Haeng
    • Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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    • v.8 no.4
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    • pp.311-318
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    • 2010
  • U. S. NRC Regulation Guide 1.52 regulating ESF ACS in nuclear power plants has been revised to revision 3. To apply reduction of operability test time, allowance of alternative challenge agents for in-place leak test of HEPA filters, and upgrade of Methyl Iodide penetration acceptance criterion in activated carbon performance test suggested in Reg. Guide 1.52(Rev.3) on Yonggwang units 5 and 6 ESF ACSes, technical feasibility study was carried out with on-site experiments as well as experiments with a lab-scale model. It was confirmed that the moisture in the system returned to the level before the test in 1 or 4 days even though the moisture was removed during the operability test lasting more than 10 hours. Therefore, it is appropriate to perform monthly operability test in 15 minutes just long enough to check the operability of equipment. To change challenge material for in-place HEPA filter leak test, size of aerosol, production rate, and leak detection capability were compared for DOP and PAO. It was concluded that PAO can be substituted for DOP in nuclear power plants. The upgrade of Methyl Iodide penetration acceptance criterion from 0.175 % to 0.5 % in active carbon filter bed deeper than 4 inches was to conform to the change of activated carbon performance test method to ASTM D3803(1989). It was confirmed that Methyl Iodide penetration acceptance criterion of 0.5 % under $30^{\circ}C$, relative humidity 95 % condition was conservatively good enough for testing performance of active carbon insitu. The licence change of Yonggwang units 5 and 6 has been completed based on this study.

Inhibition of Microbial Quorum Sensing Mediated Virulence Factors by Pestalotiopsis sydowiana

  • Parasuraman, Paramanantham;Devadatha, B;Sarma, V. Venkateswara;Ranganathan, Sampathkumar;Ampasala, Dinakara Rao;Reddy, Dhanasekhar;Kumavath, Ranjith;Kim, In-Won;Patel, Sanjay K.S.;Kalia, Vipin Chandra;Lee, Jung-Kul;Siddhardha, Busi
    • Journal of Microbiology and Biotechnology
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    • v.30 no.4
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    • pp.571-582
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    • 2020
  • Quorum sensing (QS)-mediated infections cause severe diseases in human beings. The control of infectious diseases by inhibiting QS using antipathogenic drugs is a promising approach as antibiotics are proving inefficient in treating these diseases. Marine fungal (Pestalotiopsis sydowiana PPR) extract was found to possess effective antipathogenic characteristics. The minimum inhibitory concentration (MIC) of the fungal extract against test pathogen Pseudomonas aeruginosa PAO1 was 1,000 ㎍/ml. Sub-MIC concentrations (250 and 500 ㎍/ml) of fungal extract reduced QS-regulated virulence phenotypes such as the production of pyocyanin, chitinase, protease, elastase, and staphylolytic activity in P. aeruginosa PAO1 by 84.15%, 73.15%, 67.37%, 62.37%, and 33.65%, respectively. Moreover, it also reduced the production of exopolysaccharides (74.99%), rhamnolipids (68.01%), and alginate (54.98%), and inhibited the biofilm formation of the bacteria by 90.54%. In silico analysis revealed that the metabolite of P. sydowiana PPR binds to the bacterial QS receptor proteins (LasR and RhlR) similar to their respective natural signaling molecules. Cyclo(-Leu-Pro) (CLP) and 4-Hydroxyphenylacetamide (4-HPA) were identified as potent bioactive compounds among the metabolites of P. sydowiana PPR using in silico approaches. The MIC values of CLP and 4-HPA against P. aeruginosa PAO1 were determined as 250 and 125 ㎍/ml, respectively. All the antivirulence assays were conducted at sub-MIC concentrations of CLP (125 ㎍/ml) and 4-HPA (62.5 ㎍/ml), which resulted in marked reduction in all the investigated virulence factors. This was further supported by gene expression studies. The findings suggest that the metabolites of P. sydowiana PPR can be employed as promising QS inhibitors that target pathogenic bacteria.