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81.
Heterosteroids remain interesting due to their potential biological activities. This prompted us to synthesize novel thia steroids possessing the heteroatom in the A-ring. We set out to describe a new and versatile method for preparing 3-thia steroids from cholic acid via a selective oxidation of one hydroxyl group, a Baeyer-Villiger oxidation and a photolysis as the key steps. The characteristic 1H and 13C NMR spectroscopic features of the synthesized compounds are reported. 相似文献
82.
Zheng Zhang Haijie Yu Junhao Huang Malika Faouzi Carsten Schmitz Reinhold Penner Andrea Fleig 《The Journal of biological chemistry》2014,289(8):5217-5227
The transient receptor potential melastatin member 7 (TRPM7) and member 6 (TRPM6) are divalent cation channel kinases essential for magnesium (Mg2+) homeostasis in vertebrates. It remains unclear how TRPM6 affects divalent cation transport and whether this involves functional homomeric TRPM6 plasma membrane channels or heteromeric channel assemblies with TRPM7. We show that homomeric TRPM6 is highly sensitive to intracellular free Mg2+ and therefore unlikely to be active at physiological levels of [Mg2+]i. Co-expression of TRPM7 and TRPM6 produces heteromeric TRPM7/M6 channels with altered pharmacology and sensitivity to intracellular Mg·ATP compared with homomeric TRPM7. Strikingly, the activity of heteromeric TRPM7/M6 channels is independent of intracellular Mg·ATP concentrations, essentially uncoupling channel activity from cellular energy status. Disruption of TRPM6 kinase phosphorylation activity re-introduces Mg·ATP sensitivity to the heteromeric channel similar to that of TRPM7. Thus, TRPM6 modulates the functionality of TRPM7, and the TRPM6 kinase plays a critical role in tuning the phenotype of the TRPM7·M6 channel complex. 相似文献
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84.
Malika Chegary Heleen te Brinke Jos P.N. Ruiter Frits A. Wijburg Maria S.K. Stoll Paul E. Minkler Michel van Weeghel Horst Schulz Charles L. Hoppel Ronald J.A. Wanders Sander M. Houten 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2009,1791(8):806-815
Several mouse models for mitochondrial fatty acid β-oxidation (FAO) defects have been developed. So far, these models have contributed little to our current understanding of the pathophysiology. The objective of this study was to explore differences between murine and human FAO. Using a combination of analytical, biochemical and molecular methods, we compared fibroblasts of long chain acyl-CoA dehydrogenase knockout (LCAD−/−), very long chain acyl-CoA dehydrogenase knockout (VLCAD−/−) and wild type mice with fibroblasts of VLCAD-deficient patients and human controls. We show that in mice, LCAD and VLCAD have overlapping and distinct roles in FAO. The absence of VLCAD is apparently fully compensated, whereas LCAD deficiency is not. LCAD plays an essential role in the oxidation of unsaturated fatty acids such as oleic acid, but seems redundant in the oxidation of saturated fatty acids. In strong contrast, LCAD is neither detectable at the mRNA level nor at the protein level in men, making VLCAD indispensable in FAO. Our findings open new avenues to employ the existing mouse models to study the pathophysiology of human FAO defects. 相似文献
85.
Carole Nagant Marie Tré-Hardy Malika El-Ouaaliti Paul Savage Michel Devleeschouwer Jean-Paul Dehaye 《Applied microbiology and biotechnology》2010,88(1):251-263
The bactericidal activity of a cholic acid antimicrobial derivative, CSA-13, was tested against eight strains of Pseudomonas aeruginosa (both reference and clinical strains) and compared with the response to tobramycin. In planktonic cultures, the minimal inhibitory
and minimal bactericidal concentrations of CSA-13 and tobramycin were in the 1–25 mg/L range except for one mucoid clinical
strain which was much less sensitive to tobramycin (minimal bactericidal concentration, 65–125 mg/L). In young (24 h) biofilms,
the sensitivity to CSA-13 was reduced (half-maximal concentration CSA-13 averaged 88 mg/L) and varied among the eight strains.
The sensitivity to tobramycin was also very variable among the strains and some were fully resistant to the aminoglycoside.
The combination of tobramycin with CSA-13 was synergistic in five strains. Only one strain showed antagonism between the two
drugs at low concentrations of CSA-13. One reference and five clinical strains were tested in mature (12 days) biofilms. The
effect of CSA-13 was delayed, some strains requiring 9 days exposure to the drug to observe a bactericidal effect. All the
strains were tolerant to tobramycin but the addition of CSA-13 with tobramycin was synergistic in three strains. CSA-13 permeabilized
the outer membrane of the bacteria (half-maximal concentration, 4.4 mg/L). At concentrations higher than 20 mg/L, it also
permeabilized the plasma membrane of human umbilical vein endothelial cells. In conclusion, CSA-13 has bactericidal activity
against P. aeruginosa even in mature biofilms and cationic steroid antibiotics can thus be considered as potential candidates for the treatment
of chronic pulmonary infections of patients with cystic fibrosis. Considering its interaction with the plasma membrane of
eukaryotic cells, less toxic derivatives of CSA-13 should be developed. 相似文献
86.
87.
We set out to describe a new and versatile method for preparing 3-aza-11-oxa-1,3,5(10)-trieno steroids via an intramolecular Diels-Alder cycloaddition of o-quinodimethanes as the key step. The characteristic 1H and 13C NMR spectroscopic features of the synthesized compounds are reported. 相似文献
88.
In this study, we developed an automated strategy to manufacture an enzyme BFC powered by glucose/O(2). The bioanode consists of GOx enzyme and PQQ redox mediator adsorbed over night on MWCNTs then deposited by means of AC-electrophoresis at 30 Hz and 160 V(p-p) and, finally stabilized by electropolymerized polypyrrole. The biocathode is constructed from LAc enzyme and ABTS redox mediator adsorbed over night on MWCNTs, then electrophoretically deposited under AC-electric field at 30 Hz and 160 V(p-p) and, finally stabilized by electrodeposited polypyrrole. The BFC was studied under air in phosphate buffer solution pH 7.4 containing 10 mM glucose and in human serum with 5 mM glucose addition at the physiological temperature of 37°C. Under these conditions, the maximum power density reaches 1.1 μW · mm(-2) at a cell voltage of 0.167 V in buffer solution and 0.69 μW · mm(-2) at cell voltage of 0.151 V in human serum. Such automated BFCs have a great potential to be optimized, miniaturized to micro and nanoscale devices suitable for in vivo studies. 相似文献
89.
Rémi Peyronnet Joana R Martins Fabrice Duprat Sophie Demolombe Malika Arhatte Martine Jodar Michel Tauc Christophe Duranton Marc Paulais Jacques Teulon Eric Honoré Amanda Patel 《EMBO reports》2013,14(12):1143-1148
Mechanical forces associated with fluid flow and/or circumferential stretch are sensed by renal epithelial cells and contribute to both adaptive or disease states. Non‐selective stretch‐activated ion channels (SACs), characterized by a lack of inactivation and a remarkably slow deactivation, are active at the basolateral side of renal proximal convoluted tubules. Knockdown of Piezo1 strongly reduces SAC activity in proximal convoluted tubule epithelial cells. Similarly, overexpression of Polycystin‐2 (PC2) or, to a greater extent its pathogenic mutant PC2‐740X, impairs native SACs. Moreover, PC2 inhibits exogenous Piezo1 SAC activity. PC2 coimmunoprecipitates with Piezo1 and deletion of its N‐terminal domain prevents both this interaction and inhibition of SAC activity. These findings indicate that renal SACs depend on Piezo1, but are critically conditioned by PC2. 相似文献
90.
Borbulevych O Kumarasiri M Wilson B Llarrull LI Lee M Hesek D Shi Q Peng J Baker BM Mobashery S 《The Journal of biological chemistry》2011,286(36):31466-31472
The integral membrane protein BlaR1 of methicillin-resistant Staphylococcus aureus senses the presence of β-lactam antibiotics in the milieu and transduces the information to the cytoplasm, where the biochemical events that unleash induction of antibiotic resistance mechanisms take place. We report herein by two-dimensional and three-dimensional NMR experiments of the sensor domain of BlaR1 in solution and by determination of an x-ray structure for the apo protein that Lys-392 of the antibiotic-binding site is posttranslationally modified by N(ζ)-carboxylation. Additional crystallographic and NMR data reveal that on acylation of Ser-389 by antibiotics, Lys-392 experiences N(ζ)-decarboxylation. This unique process, termed the lysine N(ζ)-decarboxylation switch, arrests the sensor domain in the activated ("on") state, necessary for signal transduction and all the subsequent biochemical processes. We present structural information on how this receptor activation process takes place, imparting longevity to the antibiotic-receptor complex that is needed for the induction of the antibiotic-resistant phenotype in methicillin-resistant S. aureus. 相似文献