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171.
172.
Inga Cikotiene Egidijus Kazlauskas Jurgita Matuliene Vilma Michailoviene Jolanta Torresan Jelena Jachno Daumantas Matulis 《Bioorganic & medicinal chemistry letters》2009,19(4):1089-1092
A series of 5-aryl-4-(5-substituted-2,4-dihydroxyphenyl)-1,2,3-thiadiazoles were synthesized and their binding to several constructs of human Hsp90 chaperone measured by isothermal titration calorimetry (ITC). The most potent compound bound Hsp90 with the dissociation constant of about 5 nM. 相似文献
173.
Adriana Rekuć Jolanta Bryjak Katarzyna Szymańska Andrzej B. Jarzębski 《Process Biochemistry》2009,44(2):191-198
Extracellular laccase produced by the wood-rotting fungus Cerrena unicolor was immobilized covalently on the mesostructured siliceous cellular foams (MCFs) functionalised using various organosilanes with amine and glycidyl groups. The experiments indicated that laccase bound via glutaraldehyde to MCFs modified using 2-aminoethyl-3-aminopropyltrimethoxysilane remains very active. In the best biocatalyst activity was about 42,700 U mL?1 carrier (66,800 U mg?1 bound protein), and hence significantly higher than ever reported before. Optimisation of the immobilization procedure with respect to protein concentration, pH of coupling mixture and the enzyme purity afforded the biocatalyst with activity of about 90,980 U mL?1. For the best preparation, thermal- and pH-stability, and activity profiles were determined. Experiments carried out in a batch reactor showed that kcat/Km for immobilized enzyme (0.88 min?1 μM?1) was acceptable lower than the value obtained for the native enzyme (2.19 min?1 μM?1). Finally, potentials of the catalysts were tested in the decolourisation of indigo carmine without redox-mediators. Seven consecutive runs with the catalysts separated by microfiltration proved that adsorption of the dye onto the carrier and enzymatic oxidation contribute to the efficient decolourisation without loss of immobilized enzyme activity. 相似文献
174.
North America is home to anuran species belonging to the families Bufonidae, Eleutherodactylidae, Hylidae, Leiopelmatidae, Ranidae, and Scaphiopodidae but antimicrobial peptides have been identified only in skin secretions and/or skin extracts of frogs belonging to the Leiopelmatidae (“tailed frogs”) and Ranidae (“true frogs”). Eight structurally-related cationic α-helical peptides with broad-spectrum antibacterial activity, termed ascaphins, have been isolated from specimens of Ascaphus truei (Leiopelmatidae) occupying a coastal range. Characterization of orthologous antimicrobial peptides from Ascaphus specimens occupying an inland range supports the proposal that this population should be regarded as a separate species A. montanus. Ascaphin-8 shows potential for development into a therapeutically valuable anti-infective agent. Peptides belonging to the brevinin-1, esculentin-1, esculentin-2, palustrin-1, palustrin-2, ranacyclin, ranatuerin-1, ranatuerin-2, and temporin families have been isolated from North American ranids. It is proposed that “ranalexins” represent brevinin-1 peptides that have undergone a four amino acid residue internal deletion. Current taxonomic recommendations divide North American frogs from the family Ranidae into two genera: Lithobates and Rana. Cladistic analysis based upon the amino acid sequences of the brevinin-1 peptides provides strong support for this assignment. 相似文献
175.
Jolanta Idkowiak-Baldys Aleksander Baldys John R. Raymond Yusuf A. Hannun 《The Journal of biological chemistry》2009,284(33):22322-22331
Considerable insight has been garnered on initial mechanisms of endocytosis of plasma membrane proteins and their subsequent trafficking through the endosomal compartment. It is also well established that ligand stimulation of many plasma membrane receptors leads to their internalization. However, stimulus-induced regulation of endosomal trafficking has not received much attention. In previous studies, we showed that sustained stimulation of protein kinase C (PKC) with phorbol esters led to sequestration of recycling endosomes in a juxtanuclear region. In this study, we investigated whether G-protein-coupled receptors that activate PKC exerted effects on endosomal trafficking. Stimulation of cells with serotonin (5-hydroxytryptamine (5-HT)) led to sequestration of the 5-HT receptor (5-HT2AR) into a Rab11-positive juxtanuclear compartment. This sequestration coincided with translocation of PKC as shown by confocal microscopy. Mechanistically the observed sequestration of 5-HT2AR was shown to require continuous PKC activity because it was inhibited by pretreatment with classical PKC inhibitor Gö6976 and could be reversed by posttreatment with this inhibitor. In addition, classical PKC autophosphorylation was necessary for receptor sequestration. Moreover inhibition of phospholipase D (PLD) activity and inhibition of PLD1 and PLD2 using dominant negative constructs also prevented this process. Functionally this sequestration did not affect receptor desensitization or resensitization as measured by intracellular calcium increase. However, the PKC- and PLD-dependent sequestration of receptors resulted in co-sequestration of other plasma membrane proteins and receptors as shown for epidermal growth factor receptor and protease activated receptor-1. This led to heterologous desensitization of those receptors and diverted their cellular fate by protecting them from agonist-induced degradation. Taken together, these results demonstrate a novel role for sustained receptor stimulation in regulation of intracellular trafficking, and this process requires sustained stimulation of PKC and PLD.The protein kinase C (PKC)2 family of enzymes comprises 11 isoforms of serine/threonine kinases (1, 2) implicated in regulation of cell growth, differentiation, apoptosis, secretion, neurotransmission, and signal transduction (3–5). During the course of studying PKC, we showed that sustained stimulation of PKC with phorbol esters leads to translocation of classical PKC (cPKC) to a pericentrosomal region (6, 7). This sequestration was shown to be PLD-dependent (8, 9) and negatively regulated by ceramide formed from the salvage pathway (10). Ceramide inhibits autophosphorylation of cPKC, which was also found to be required for this novel translocation (11). Importantly sustained activation of cPKC also resulted in significant effects on recycling components and their sequestration to the same region, dubbed the pericentrion (defined as the cPKC-dependent subset of recycling endosomes). On the other hand, components and markers of the endolysosomal compartment were not sequestered to the pericentrion upon PKC stimulation (7). Functionally it was also shown that pericentrion formation and sequestration of PKC requires clathrin-dependent endocytosis. Most importantly, formation of the pericentrion is dynamic and reversible and requires continuous activation of PKC.G-protein-coupled receptors (GPCRs) are the largest family of integral membrane receptors. They contain seven transmembrane domains (12), are coupled to heterotrimeric G-proteins, and are activated by a vast number of ligands. They regulate many cellular processes and serve as targets for at least half of the therapeutics currently present on the market. Upon agonist binding, conformational changes in the receptor lead to coupling with G-proteins (composed of α, β, and γ subunits). This leads to dissociation of α and β/γ subunits that mediate downstream signaling (13). Interestingly PKC serves as one of the downstream targets of GPCRs. Thus, it became critical to determine whether persistent stimulation of receptors that couple to cPKC exerts effects on recycling endosomes. We focused on the serotonin (5-HT) 5-HT2A receptor (5-HT2AR) and the angiotensin II receptor (AT1AR) as two GPCRs that couple to Gq, which in turn activates phospholipase Cβ and then PKC (14, 15).In this study, we show that sustained stimulation of those receptors led to their sequestration in a PKC- and PLD-dependent manner. Most importantly, this led to global sequestration of endosomes with profound effects on other membrane receptors. Epidermal growth factor receptor (EGFR) and protease activated receptor-1 (PAR-1) are known to be targeted into a degradative pathway upon their agonist treatment (16–18). Interestingly 5-HT induced co-sequestration of those receptors with 5-HT2AR and protected them from degradation upon their own agonist treatment. The implications of these results on regulation of trafficking by GPCRs are discussed. 相似文献
176.
Gianna Moscato Olivier Vandenplas Roy Gerth Van Wijk Jean-Luc Malo Luca Perfetti Santiago Quirce Jolanta Walusiak Roberto Castano Gianni Pala Denyse Gautrin Hans De Groot Ilenia Folletti Mona Rita Yacoub Andrea Siracusa 《Respiratory research》2009,10(1):1-20
The present document is the result of a consensus reached by a panel of experts from European and non-European countries on Occupational Rhinitis (OR), a disease of emerging relevance which has received little attention in comparison to occupational asthma. The document covers the main items of OR including epidemiology, diagnosis, management, socio-economic impact, preventive strategies and medicolegal issues. An operational definition and classification of OR tailored on that of occupational asthma, as well as a diagnostic algorithm based on steps allowing for different levels of diagnostic evidence are proposed. The needs for future research are pointed out. Key messages are issued for each item. 相似文献
177.
Delphine Milhas Christopher J. Clarke Jolanta Idkowiak-Baldys Daniel Canals Yusuf A. Hannun 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2010,1801(12):1361-1374
The activation of neutral sphingomyelinase-2 (nSMase2) and consequent ceramide production are implicated in many stress-induced signaling pathways. Trafficking of nSMase2 from the Golgi compartment to the plasma membrane (PM) in response to signaling stimuli has been described. However, the precise mechanisms of transport remain unknown. This study aimed to investigate the trafficking of nSMase2 between the Golgi and the PM. We show here that V5-nSMase2 localizes at the PM and Golgi in MCF-7 cells and confirm relocalization of nSMase2 to the PM at confluence. Although cycloheximide (CHX) treatment partially inhibited the Golgi localization of GFP-nSMase2, recovery of GFP-nSMase2 to an intracellular compartment was still observed after photobleaching. Moreover, in the presence of CHX, GFP- and V5-nSMase2 co-localized with endosomal/recycling markers. In HEK293 cells, activation of either protein kinase C-alpha or betaII, with the phorbol ester PMA led to relocalization of both wild-type and inactive nSMase2 to the pericentrion, a PKC-dependent subset of recycling endosomes. Finally, inhibition of nSMase2 endocytosis by K + depletion reduced the intracellular pool of nSMase2 and increased nSMase2 activity resulting in elevated ceramide levels. Altogether, these results suggest that nSMase2 traffics from the Golgi to the PM as a membrane protein en route to the cell surface and recycles back to the Golgi through the endosomal/recycling compartment. Moreover, the recycling of nSMase2 from the PM is important for its catalytic regulation. 相似文献
178.
179.
Magdalena Arasimowicz-Jelonek Jolanta Floryszak-Wieczorek Kinga Drzewiecka Jagna Chmielowska-Bąk Dariusz Abramowski Karolina Izbiańska 《Planta》2014,239(3):679-694
The phenomenon of cross-resistance allows plants to acquire resistance to a broad range of stresses after previous exposure to one specific factor. Although this stress–response relationship has been known for decades, the sequence of events that underpin cross-resistance remains unknown. Our experiments revealed that susceptible potato (Solanum tuberosum L. cv. Bintje) undergoing aluminum (Al) stress at the root level showed enhanced defense responses correlated with reduced disease symptoms after leaf inoculation with Phytophthora infestans. The protection capacity of Al to subsequent stress was associated with the local accumulation of H2O2 in roots and systemic activation of salicylic acid (SA) and nitric oxide (NO) dependent pathways. The most crucial Al-mediated changes involved coding of NO message in an enhanced S-nitrosothiol formation in leaves tuned with an abundant SNOs accumulation in the main vein of leaves. Al-induced distal NO generation was correlated with the overexpression of PR-2 and PR-3 at both mRNA and protein activity levels. In turn, after contact with a pathogen we observed early up-regulation of SA-mediated defense genes, e.g. PR1, PR-2, PR-3 and PAL, and subsequent disease limitation. Taken together Al exposure induced distal changes in the biochemical stress imprint, facilitating more effective responses to a subsequent pathogen attack. 相似文献
180.