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51.
Stoop R Albrecht D Gaissmaier C Fritz J Felka T Rudert M Aicher WK 《Arthritis research & therapy》2007,9(3):R60
Currently, autologous chondrocyte transplantation (ACT) is used to treat traumatic cartilage damage or osteochondrosis dissecans,
but not degenerative arthritis. Since substantial refinements in the isolation, expansion and transplantation of chondrocytes
have been made in recent years, the treatment of early stage osteoarthritic lesions using ACT might now be feasible. In this
study, we determined the gene expression patterns of osteoarthritic (OA) chondrocytes ex vivo after primary culture and subculture and compared these with healthy chondrocytes ex vivo and with articular chondrocytes expanded for treatment of patients by ACT. Gene expression profiles were determined using
quantitative RT-PCR for type I, II and X collagen, aggrecan, IL-1β and activin-like kinase-1. Furthermore, we tested the capability
of osteoarthritic chondrocytes to generate hyaline-like cartilage by implanting chondrocyte-seeded collagen scaffolds into
immunodeficient (SCID) mice. OA chondrocytes ex vivo showed highly elevated levels of IL-1β mRNA, but type I and II collagen levels were comparable to those of healthy chondrocytes.
After primary culture, IL-1β levels decreased to baseline levels, while the type II and type I collagen mRNA levels matched
those found in chondrocytes used for ACT. OA chondrocytes generated type II collagen and proteoglycan-rich cartilage transplants
in SCID mice. We conclude that after expansion under suitable conditions, the cartilage of OA patients contains cells that
are not significantly different from those from healthy donors prepared for ACT. OA chondrocytes are also capable of producing
a cartilage-like tissue in the in vivo SCID mouse model. Thus, such chondrocytes seem to fulfil the prerequisites for use in ACT treatment. 相似文献
52.
Hortencia Silva‐Jiménez Álvaro Ortega Cristina García‐Fontana Juan Luis Ramos Tino Krell 《Microbial biotechnology》2015,8(1):103-115
The reason for the existence of complex sensor kinases is little understood but thought to lie in the capacity to respond to multiple signals. The complex, seven‐domain sensor kinase TodS controls in concert with the TodT response regulator the expression of the toluene dioxygenase pathway in Pseudomonas putida F1 and DOT‐T1E. We have previously shown that some aromatic hydrocarbons stimulate TodS activity whereas others behave as antagonists. We show here that TodS responds in addition to the oxidative agent menadione. Menadione but no other oxidative agent tested inhibited TodS activity in vitro and reduced PtodX expression in vivo. The menadione signal is incorporated by a cysteine‐dependent mechanism. The mutation of the sole conserved cysteine of TodS (C320) rendered the protein insensitive to menadione. We evaluated the mutual opposing effects of toluene and menadione on TodS autophosphorylation. In the presence of toluene, menadione reduced TodS activity whereas toluene did not stimulate activity in the presence of menadione. It was shown by others that menadione increases expression of glucose metabolism genes. The opposing effects of menadione on glucose and toluene metabolism may be partially responsible for the interwoven regulation of both catabolic pathways. This work provides mechanistic detail on how complex sensor kinases integrate different types of signal molecules. 相似文献
53.
Segura A Molina L Fillet S Krell T Bernal P Muñoz-Rojas J Ramos JL 《Current opinion in biotechnology》2012,23(3):415-421
Bacteria have been found in all niches explored on Earth, their ubiquity derives from their enormous metabolic diversity and their capacity to adapt to changes in the environment. Some bacterial strains are able to thrive in the presence of high concentrations of toxic organic chemicals, such as aromatic compounds, aliphatic alcohols and solvents. The extrusion of these toxic compounds from the cell to the external medium represents the most relevant aspect in the solvent tolerance of bacteria, however, solvent tolerance is a multifactorial process that involves a wide range of genetic and physiological changes to overcome solvent damage. These additional elements include reduced membrane permeabilization, implementation of a stress response programme, and in some cases degradation of the toxic compound. We discuss the recent advances in our understanding of the mechanisms involved in solvent tolerance. 相似文献
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55.
The RND family transporter TtgABC and its cognate repressor TtgR from Pseudomonas putida DOT-T1E were both shown to possess multidrug recognition properties. Structurally unrelated molecules such as chloramphenicol, butyl paraben, 1,3-dihydroxynaphthalene, and several flavonoids are substrates of TtgABC and activate pump expression by binding to the TtgR-operator complex. Isothermal titration calorimetry was employed to determine the thermodynamic parameters for the binding of these molecules to TtgR. Dissociation constants were in the range from 1 to 150 microm, the binding stoichiometry was one effector molecule per dimer of TtgR, and the process was driven by favorable enthalpy changes. Although TtgR exhibits a large multidrug binding profile, the plant-derived compounds phloretin and quercetin were shown to bind with the highest affinity (K(D) of around 1 microm), in contrast to other effectors (chloramphenicol and aromatic solvents) for which exhibited a more reduced affinity. Structure-function studies of effectors indicate that the presence of aromatic rings as well as hydroxyl groups are determinants for TtgR binding. The binding of TtgR to its operator DNA does not alter the protein effector profile nor the effector binding stoichiometry. Moreover, we demonstrate here for the first time that the binding of a single effector molecule to the DNA-bound TtgR homodimer induces the dissociation of the repressor-operator complex. This provides important insight into the molecular mechanism of effector-mediated derepression. 相似文献
56.
57.
Anna Kärkönen Tino Warinowski Teemu H. Teeri Liisa Kaarina Simola Stephen C. Fry 《Planta》2009,230(3):553-567
A cell culture of Picea abies (L.) Karst. was used for studies of H2O2 generation during constitutive extracellular lignin formation and after elicitation by cell wall fragments of a pathogenic
fungus, Heterobasidium parviporum. Stable, micromolar levels of H2O2 were present in the culture medium during lignin formation. Elicitation induced a burst of H2O2, peaking at ca. 90 min after elicitation. Of exogenous reducing substrates that may be responsible for the synthesis of H2O2 from O2, NADH stimulated H2O2 production irrespective of elicitation. Cysteine (Cys) and glutathione (GSH) partially scavenged the constitutive H2O2, but usually increased or prolonged elicitor-induced H2O2 formation. Culture medium peroxidases were not able to generate H2O2 in vitro with Cys or GSH as reductants. These thiols, however, generated H2O2 non-enzymically at pH 4.5. [35S]Sulphate feeding to spruce cells showed that endogenous sulphur-containing compounds (including GSH, GSSG and cysteic acid)
existed in the culture medium. The apoplastic levels of these were, however, undetectable by the monobromobimane method suggesting
that their contribution to apoplastic H2O2 formation is probably minor. Azide, an inhibitor of haem-containing enzymes, slightly inhibited constitutive H2O2 generation but strongly delayed the elicitor-induced H2O2 accumulation. Diphenylene iodonium, an inhibitor of flavin-containing enzymes, efficiently inhibited H2O2 production irrespective of elicitation. Elicitation led to downregulation of the expression of several peroxidase genes,
and peroxidase activity in the culture medium was slightly reduced. Expression of three other peroxidase genes and a respiratory burst oxidase homologue (rboh) gene were upregulated. These data suggest that both peroxidases and rboh may contribute to H2O2 generation.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
58.
Peng Wang Chuan Liu Tino Sanches Yuan Zhong Bo Liu Junlong Xiong Nouri Neamati Guisen Zhao 《Bioorganic & medicinal chemistry letters》2009,19(16):4574-4578
A series of nitrogen-containing polyhydroxylated aromatics from caffeic acid phenethyl ester were designed and synthesized as HIV-1 integrase inhibitors. Most of these compounds exhibited potent inhibitory activities at micromolar concentrations against HIV-1 integrase in the 3′-end processing and the strand transfer. Their key structure–activity relationship was also discussed. 相似文献
59.
Jürgen Scherkenbeck Horst‐Peter Antonicek Kathrin Vogelsang Tino Zdobinsky Karin Brücher Denise Rehländer Heru Chen 《Journal of peptide science》2009,15(11):783-789
Neuropeptides control numerous physiological processes in insects. The regulation of water balance is a crucial aspect of homeostasis in terrestrial insects and has been shown to be under endocrine control, primarily by corticotrophin releasing factor (CRF)‐related peptides and kinins. For helicokinin I, a diuretic neuropeptide from the economically important insect pest Heliothis virescens, detailed structure‐activity relationships have been established based on truncated structures, diverse amino acid scans and peptidomimetic analogues. The activities of selected compounds on functional expressed helicokinin receptors are compared with the results of a Malphigian tubule assay. Implications for further peptidomimetic variations are provided. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
60.
Lysosomes contain most of the cell's supply of labile iron, which makes them sensitive to oxidative stress. To keep lysosomal labile iron at a minimum, a cellular strategy might be to autophagocytose iron binding proteins that temporarily would chelate iron in a non-redox-active form. Previously we have shown that autophagy of metallothioneins, as well as of non-Fe-saturated ferritin, meets this goal. Here we add another stress-regulated protein to the list, namely HSP70. 相似文献