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971.
972.
Dürrschmid K Reischer H Schmidt-Heck W Hrebicek T Guthke R Rizzi A Bayer K 《Journal of biotechnology》2008,135(1):34-44
The use of strong promoter systems for recombinant protein production generates high product yields, but also overburdens the host cell metabolism and compromises production. Escherichia coli has highly developed regulatory pathways that are immediately responsive to adverse conditions. To gain insight into stress response mechanisms and to detect marker genes and proteins for stress specific monitoring time course analysis of controlled chemostat cultivations was performed using E. coli total microarray and difference gel electrophoresis (Ettan™ DIGE). In order to detect differences and consistencies of stress response as well as the impact of the inducer isopropyl-β-d-thiogalactopyranosid on cells, expression of two recombinant proteins (hSOD and GFPmut3.1) was investigated. Genes involved in aerobic metabolism under control of the ArcB/ArcA two component system were found to be down-regulated, and the interplay of the psp operon, ArcA system and guanosine tetraphosphate is suggested to be involved in stress regulatory mechanisms. A distinct impact of the two recombinant proteins was observed, particularly on levels of known stress regulatory genes and proteins, as well as on the response associated with ArcA and psp. Altogether, 62 genes as well as seven proteins showed consistent expression levels due to recombinant gene expression, and are therefore suggested to be appropriate monitoring targets. 相似文献
973.
The polycyclic aromatic hydrocarbon (PAH) benzo[ghi]perylene (BghiP) lacks a "classic" bay-region and is therefore unable to form vicinal dihydrodiol epoxides thought to be responsible for the genotoxicity of carcinogenic PAHs like benzo[a]pyrene. The bacterial mutagenicity of BghiP increases considerably after inhibition of the microsomal epoxide hydrolase (mEH) indicating arene oxides as genotoxic metabolites. Two K-region epoxides of BghiP, 3,4-epoxy-3,4-dihydro-BghiP (3,4-oxide) and 3,4,11,12-bisepoxy-3,4,11,12-tetrahydro-BghiP (3,4,11,12-bisoxide) identified in microsomal incubations of BghiP are weak bacterial mutagens in strain TA98 of Salmonella typhimurium with 5.5 and 1.5 his+-revertant colonies/nmol, respectively. After microsomal activation of BghiP in the presence of calf thymus DNA three DNA adducts were detected using 32P-postlabeling. The total DNA binding of 2.1 fmol/microg DNA, representing 7 adducts in 10(7) nucleotides, was raised 3.6-fold when mEH was inhibited indicating arene oxides as DNA binding metabolites. Co-chromatography revealed the identity between the main adduct of metabolically activated BghiP and the main adduct of the 3,4-oxide. DNA adducts of BghiP originating from the 3,4,11,12-bisoxide were not found. Therefore, a K-region epoxide is proposed to be responsible for the genotoxicity of BghiP and possibly of other PAHs without a "classic" bay-region. 相似文献
974.
975.
976.
Antifreeze proteins are a structurally diverse group of proteins characterized by their unique ability to cause a separation of the melting- and growth-temperatures of ice. These proteins have evolved independently in different kinds of cold-adapted ectothermic animals, including insects and fish, where they protect against lethal freezing of the body fluids. There is a great variability in the capacity of different kinds of antifreeze proteins to evoke the antifreeze effect, but the basis of these differences is not well understood. This study reports on salt-induced enhancement of the antifreeze activity of an antifreeze protein from the longhorn beetle Rhagium inquisitor (L.). The results imply that antifreeze activity is predetermined by a steady-state distribution of the antifreeze protein between the solution and the ice surface region. The observed salt-induced enhancement of the antifreeze activity compares qualitatively and quantitatively with salt-induced lowering of protein solubility. Thus, salts apparently enhance antifreeze activity by evoking a solubility-induced shift in the distribution pattern of the antifreeze proteins in favour of the ice. These results indicate that the solubility of antifreeze proteins in the solution surrounding the ice crystal is a fundamental physiochemical property in relation to their antifreeze potency. 相似文献
977.
In living cells, P2Y(1) receptor dimerization was quantitated by an improved version of fluorescence resonance energy transfer donor photobleaching analysis. 44% of the P2Y(1) receptors expressed in HEK293 cell membranes exist as dimers in the resting state, inducible by agonist exposure to give 85-100% dimerization. Monomer and constitutive dimers are fully active. Agonist-induced dimerization follows desensitization and is fully reversible upon withdrawal of agonist. Receptor dimers are required for internalization at 37 degrees C but are not sufficient; at 20 degrees C dimerization also occurs, but endocytosis is abolished. Removal of the C-terminal 19 amino acids abolished both dimerization and internalization, whereas full activation by agonists was retained up to a loss of 39 amino acids, confirming active monomers. This receptor is known to bind through its last four amino acids (DTSL) to a scaffolding protein, Na/H exchanger regulatory factor-2, which was endogenous here, and DTSL removal blocked constitutive dimerization specifically. Distinction should therefore be made between the following: 1) constitutive dimers tethered to a scaffolding protein, together with effector proteins, within a signaling micro-domain, and 2) free dimers in the cell membrane, which here are inducible by agonist exposure. For the class A G-protein-coupled receptors, we suggest that the percentages of free monomers, and in many cases of induced free dimers, commonly become artifactually increased; this would arise from an excess there of the receptor over its specific scaffold and from a lack of the native targeting of the receptor to that site. 相似文献
978.
On the occasion of the first international workshop on systems radiation biology we review the role of cell renewal systems
in maintaining the integrity of the mammalian organism after irradiation. First, 11 radiation emergencies characterized by
chronic or protracted exposure of the human beings to ionizing irradiation were “revisited”. The data provide evidence to
suggest that at a daily exposure of about 10–100 mSv, humans are capable of coping with the excess cell loss for weeks or
even many months without hematopoietic organ failure. Below 10 mSv/day, the organisms show some cellular or subcellular indicators
of response. At dose rates above 100 mSv/day, a progressive shortening of the life span of the irradiated organism is observed.
To elucidate the mechanisms relevant to tolerance or failure, the Megakaryocyte–thrombocyte cell renewal system was investigated.
A biomathematical model of this system was developed to simulate the development of thrombocyte concentration as a function
of time after onset of chronic radiation exposure. The hematological data were taken from experimental chronic irradiation
studies with dogs at the Argonne National Laboratory, USA. The results of thrombocyte response patterns are compatible with
the notion of an “excess cell loss” (compared to the steady-state) in all proliferative cell compartments, including the stem
cell pool. The “excess cell loss” is a function of the daily irradiation dose rate. Once the stem cell pool is approaching
an exhaustion level, a “turbulence region” is reached. Then it takes a very little additional stress for the system to fail.
We conclude that in mammalian radiation biology (including radiation medicine), it is important to understand the physiology
and pathophysiology of cell renewal systems in order to allow predicting the development of radiation induced lesions. 相似文献
979.
980.