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31.
Jaresová I Rozková D Spísek R Janda A Brázová J Sedivá A 《Microbes and infection / Institut Pasteur》2007,9(11):1359-1367
Toll-like receptors (TLR) are key components of innate immune system. As TLR activation could induce potentially harmful inflammatory response, activation of TLR signaling pathways has to be under tight control. Besides other control mechanisms, an inhibitory function of murine TLR4 splice variants was recently demonstrated. In this study we investigated expression of four TLR4 splice variants in human antigen presenting cells (APC). Furthermore, we studied modification in TLR4 splice variants expression in APC in cystic fibrosis (CF) patients chronically infected by Gram-negative bacteria. We developed a novel reliable real-time PCR detection system that allowed monitoring of individual TLR4 splice variants expression. In APC from healthy donors we detected a characteristic transient increase of two out of four splice variants after lipopolysaccharide (LPS) stimulation. Similarly to murine TLR4, one of these variants, NM 003266, might translate to a potentially inhibitory protein. In contrast to controls, CF monocytes had significantly changed LPS-induced expression of TLR4 gene and its variants including reduced ability to up-regulate the expression of the potentially inhibitory variant upon stimulation. In accordance with this observation, monocytes from CF patients produced significantly more tumor necrosis factor after LPS stimulation than healthy controls. Our results thus describe the kinetics of TLR4 splicing variants expression after LPS stimulation and indicate a possible alteration of its regulation in CF patients. 相似文献
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Sailendra N. Nichenametla Dwight A. L. Mattocks Diana Cooke Vishal Midya Virginia L. Malloy Wilfredo Mansilla Bente
vreb Cheryl Turner Nasser
E. Bastani Jitka Sokolov Markta Pavlíkov John P. Richie Jr. Anna
K. Shoveller Helga Refsum Thomas Olsen Kathrine J. Vinknes Viktor Koich Gene P. Ables 《Aging cell》2022,21(12)
Decreasing the dietary intake of methionine exerts robust anti‐adiposity effects in rodents but modest effects in humans. Since cysteine can be synthesized from methionine, animal diets are formulated by decreasing methionine and eliminating cysteine. Such diets exert both methionine restriction (MR) and cysteine restriction (CR), that is, sulfur amino acid restriction (SAAR). Contrarily, SAAR diets formulated for human consumption included cysteine, and thus might have exerted only MR. Epidemiological studies positively correlate body adiposity with plasma cysteine but not methionine, suggesting that CR, but not MR, is responsible for the anti‐adiposity effects of SAAR. Whether this is true, and, if so, the underlying mechanisms are unknown. Using methionine‐ and cysteine‐titrated diets, we demonstrate that the anti‐adiposity effects of SAAR are due to CR. Data indicate that CR increases serinogenesis (serine biosynthesis from non‐glucose substrates) by diverting substrates from glyceroneogenesis, which is essential for fatty acid reesterification and triglyceride synthesis. Molecular data suggest that CR depletes hepatic glutathione and induces Nrf2 and its downstream targets Phgdh (the serine biosynthetic enzyme) and Pepck‐M. In mice, the magnitude of SAAR‐induced changes in molecular markers depended on dietary fat concentration (60% fat >10% fat), sex (males > females), and age‐at‐onset (young > adult). Our findings are translationally relevant as we found negative and positive correlations of plasma serine and cysteine, respectively, with triglycerides and metabolic syndrome criteria in a cross‐sectional epidemiological study. Controlled feeding of low‐SAA, high‐polyunsaturated fatty acid diets increased plasma serine in humans. Serinogenesis might be a target for treating hypertriglyceridemia. 相似文献
35.
We experimentally demonstrated the ability of three short-lived monocarpic species to vegetatively regenerate (resprout) from
roots after severe disturbance. We assessed the relationship between resprouting ability and (1) timing of injury with respect
to life-cycle stage (reproductive vs. vegetative plant), life-history mode (annual vs. winter annual) and phenological stage
(flowering vs. fruiting plant), (2) nutrient availability, and (3) disturbance severity (removal of all axillary buds Yes/No).
In a chamber experiment with the annual or potentially winter annualRorippa palustris, all injured plants resprouted in all nutrient levels and day-length regimes (day-length regimes simulated conditions of
an annual and a winter annual cohort). The number of adventitious buds on roots was positively affected only by injury. The
extent of regeneration and amount of regenerated biomass were higher at high nutrient level and long-day regime. 相似文献
36.
Poljaková J Forsterová K Sulc M Frei E Stiborová M 《Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia》2005,149(2):449-453
Ellipticine is a potent antineoplastic agent, whose mode of action is considered to be based mainly on DNA intercalation and/or inhibition of topoisomerase II. Since we found that ellipticine also forms the cytochrome P450 (CYP)-mediated covalent DNA adducts, this anticancer drug is considered to function as a pro-drug, whose pharmacological efficiency and/or genotoxic side effects are dependent on its enzymatic activation in target tissues. Here, we demonstrate that ellipticine is also oxidized by peroxidases, which are abundantly expressed in several target tumor tissues. Lactoperoxidase, myeloperoxidase and horseradish peroxidase were used as models. Peroxidases in the presence of hydrogen peroxide oxidize ellipticine to an ellipticine dimer and N(2)-oxide of ellipticine as the major and minor metabolite, respectively. Inhibition of the peroxidase-mediated ellipticine oxidation by radical scavengers ascorbate, glutathione and NADH suggests a one-electron mechanism of the oxidation. The implication of the oxidation of ellipticine by peroxidases in its mechanism of action is discussed. 相似文献
37.
Petrlová J Blastík O Průsa R Kukacka J Potĕsil D Mikelová R Adam V Zehnálek J Kizek R 《Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia》2005,149(2):485-488
Metallothioneins belong to the group of intracellular, high molecular and cysteine-rich proteins whose content increase with increasing concentration of a heavy metal. Here we applied the adsorptive transfer stripping differential pulse voltammetry Brdicka reaction for the determination of metallothionein in human blood serum of patient poisoned by lead and/or treated by platinum. The increased metallothionein concentrations in both cases were observed. 相似文献
38.
Background and Aims
Adventitious sprouting from the hypocotyle and roots in monocarpic herbs has been confirmed in previous experimental studies as a means to avoid bud limitation after severe injury in annual and biennial plants. Data regarding the role of adventitious sprouting in natural populations, however, were lacking. The aim of the present study was to assess whether adventitious sprouting occurs in natural populations and how it is affected by plant size, plant injury, plant cover and environmental characteristics.Methods
Data were sampled from 14 037 individual plants from 389 populations belonging to 22 annual and biennial species. Growth parameters were measured in individual plants, species composition and plant cover in communities were evaluated, and environmental characteristics were estimated using Ellenberg indicator values.Key Results
It was confirmed that adventitious sprouting occurs in natural populations of all but five species examined. Adventitious sprouting was positively affected by plant size and plant injury. Environmental factors including availability of soil nitrogen were not shown to affect adventitious sprouting. Annual and biennial plants did not differ in sprouting, but upright annuals had a lower number of and longer adventitious shoots than prostrate annuals.Conclusions
Adventitious bud formation is used to overcome meristem limitation when stem parts are lost due to injury, and thus resprouting in short-lived monocarps should not be overlooked. 相似文献39.
40.
Jobin Varkey Jose Mario Isas Naoko Mizuno Martin Borch Jensen Vikram Kj?ller Bhatia Christine C. Jao Jitka Petrlova John C. Voss Dimitrios G. Stamou Alasdair C. Steven Ralf Langen 《The Journal of biological chemistry》2010,285(42):32486-32493
Synucleins and apolipoproteins have been implicated in a number of membrane and lipid trafficking events. Lipid interaction for both types of proteins is mediated by 11 amino acid repeats that form amphipathic helices. This similarity suggests that synucleins and apolipoproteins might have comparable effects on lipid membranes, but this has not been shown directly. Here, we find that α-synuclein, β-synuclein, and apolipoprotein A-1 have the conserved functional ability to induce membrane curvature and to convert large vesicles into highly curved membrane tubules and vesicles. The resulting structures are morphologically similar to those generated by amphiphysin, a curvature-inducing protein involved in endocytosis. Unlike amphiphysin, however, synucleins and apolipoproteins do not require any scaffolding domains and curvature induction is mediated by the membrane insertion and wedging of amphipathic helices alone. Moreover, we frequently observed that α-synuclein caused membrane structures that had the appearance of nascent budding vesicles. The ability to function as a minimal machinery for vesicle budding agrees well with recent findings that α-synuclein plays a role in vesicle trafficking and enhances endocytosis. Induction of membrane curvature must be under strict regulation in vivo; however, as we find it can also cause disruption of membrane integrity. Because the degree of membrane curvature induction depends on the concerted action of multiple proteins, controlling the local protein density of tubulating proteins may be important. How cellular safeguarding mechanisms prevent such potentially toxic events and whether they go awry in disease remains to be determined. 相似文献