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Deciphering preferential interactions within supramolecular protein complexes: the proteasome case 下载免费PDF全文
Bertrand Fabre Thomas Lambour Luc Garrigues François Amalric Nathalie Vigneron Thomas Menneteau Alexandre Stella Bernard Monsarrat Benoît Van den Eynde Odile Burlet‐Schiltz Marie‐Pierre Bousquet‐Dubouch 《Molecular systems biology》2015,11(1)
In eukaryotic cells, intracellular protein breakdown is mainly performed by the ubiquitin–proteasome system. Proteasomes are supramolecular protein complexes formed by the association of multiple sub-complexes and interacting proteins. Therefore, they exhibit a very high heterogeneity whose function is still not well understood. Here, using a newly developed method based on the combination of affinity purification and protein correlation profiling associated with high-resolution mass spectrometry, we comprehensively characterized proteasome heterogeneity and identified previously unknown preferential associations within proteasome sub-complexes. In particular, we showed for the first time that the two main proteasome subtypes, standard proteasome and immunoproteasome, interact with a different subset of important regulators. This trend was observed in very diverse human cell types and was confirmed by changing the relative proportions of both 20S proteasome forms using interferon-γ. The new method developed here constitutes an innovative and powerful strategy that could be broadly applied for unraveling the dynamic and heterogeneous nature of other biologically relevant supramolecular protein complexes. 相似文献
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Tania van Laer Peter de Smedt Frederik Ronsse Greet Ruysschaert Pascal Boeckx Willy Verstraete Jeroen Buysse Luc J. Lavrysen 《Global Change Biology Bioenergy》2015,7(1):14-24
This article addresses biochar from a legal point of view. It analyses different policies and regulations from a European (Flemish) point of view and provides a first and general insight in what potential legal constraints the development of a biochar industry might face and what opportunities lie ahead. This is due to the fact that biochar is a recent product and a lot of scientific uncertainty still exists regarding the consequences of its application. From the analysis it appears a multitude of policies and legislative measures influence the development of the biochar industry. Hence, it is important that all these policies and legislative measures are analyzed in an appropriate manner. Moreover, considerable lobbying, negotiating and cooperation between different disciplines (legal, scientific, economical, etc.) will be required so as to develop a feasible and safe biochar framework. 相似文献
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Neurosteroids can modulate the activity of the GABAA receptors, and thus affect anxiety-like behaviors. The non-benzodiazepine anxiolytic compound etifoxine has been shown to increase neurosteroid concentrations in brain tissue but the mode of action of etifoxine on neurosteroid formation has not yet been elucidated. In the present study, we have thus investigated the effect and the mechanism of action of etifoxine on neurosteroid biosynthesis using the frog hypothalamus as an experimental model. Exposure of frog hypothalamic explants to graded concentrations of etifoxine produced a dose-dependent increase in the biosynthesis of 17-hydroxypregnenolone, dehydroepiandrosterone, progesterone and tetrahydroprogesterone, associated with a decrease in the production of dihydroprogesterone. Time-course experiments revealed that a 15-min incubation of hypothalamic explants with etifoxine was sufficient to induce a robust increase in neurosteroid synthesis, suggesting that etifoxine activates steroidogenic enzymes at a post-translational level. Etifoxine-evoked neurosteroid biosynthesis was not affected by the central-type benzodiazepine (CBR) receptor antagonist flumazenil, the translocator protein (TSPO) antagonist PK11195 or the GABAA receptor antagonist bicuculline. In addition, the stimulatory effects of etifoxine and the triakontatetraneuropeptide TTN, a TSPO agonist, were additive, indicating that these two compounds act through distinct mechanisms. Etifoxine also induced a rapid stimulation of neurosteroid biosynthesis from frog hypothalamus homogenates, a preparation in which membrane receptor signalling is disrupted. In conclusion, the present study demonstrates that etifoxine stimulates neurosteroid production through a membrane receptor-independent mechanism. 相似文献
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Marta Simó Pablo Ripollés Lluís Fuentemilla Lucía Vaquero Jordi Bruna Antoni Rodríguez-Fornells 《PloS one》2015,10(3)
The medial temporal lobe (MTL)—comprising hippocampus and the surrounding neocortical regions—is a targeted brain area sensitive to several neurological diseases. Although functional magnetic resonance imaging (fMRI) has been widely used to assess brain functional abnormalities, detecting MTL activation has been technically challenging. The aim of our study was to provide an fMRI paradigm that reliably activates MTL regions at the individual level, thus providing a useful tool for future research in clinical memory-related studies. Twenty young healthy adults underwent an event-related fMRI study consisting of three encoding conditions: word-pairs, face-name associations and complex visual scenes. A region-of-interest analysis at the individual level comparing novel and repeated stimuli independently for each task was performed. The results of this analysis yielded activations in the hippocampal and parahippocampal regions in most of the participants. Specifically, 95% and 100% of participants showed significant activations in the left hippocampus during the face-name encoding and in the right parahippocampus, respectively, during scene encoding. Additionally, a whole brain analysis, also comparing novel versus repeated stimuli at the group level, showed mainly left frontal activation during the word task. In this group analysis, the face-name association engaged the HP and fusiform gyri bilaterally, along with the left inferior frontal gyrus, and the complex visual scenes activated mainly the parahippocampus and hippocampus bilaterally. In sum, our task design represents a rapid and reliable manner to study and explore MTL activity at the individual level, thus providing a useful tool for future research in clinical memory-related fMRI studies. 相似文献
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Eveline Dirinck Philippe G. Jorens Adrian Covaci Tinne Geens Laurence Roosens Hugo Neels Ilse Mertens Luc van Gaal 《Obesity (Silver Spring, Md.)》2011,19(4):709-714
Persistent organic pollutants (POPs) are endocrine‐disrupting chemicals associated with the development of the metabolic syndrome and type 2 diabetes. In humans, little is known about their role in the potential origin of obesity. This study aims to assess the associations between serum levels of POPs and the prevalence of obesity in a cohort of obese and lean adult men and women. POP serum samples were investigated cross‐sectionally in 98 obese and 47 lean participants, aged ≥18 years. Serum samples were analyzed for the presence of polychlorinated biphenyl (PCB) congeners 153, 138, 180, and 170 and for the organochlorine pesticides, dichloro‐diphenyl‐dichloroethylene (pp‐DDE), and β‐hexachlorocyclohexane (βHCH). We established a significant negative correlation between BMI, waist, fat mass percentage, total and subcutaneous abdominal adipose tissue, and serum levels of PCB 153, 180, 170, and the sumPCBs. For βHCH, we demonstrated a positive correlation with BMI, waist, fat mass percentage, and total and subcutaneous abdominal adipose tissue. PCBs 180, 170, and the sum of PCBs correlated significantly negative with homeostasis model assessment for insulin resistance (HOMAIR). βHCH correlated significantly positively with HOMAIR. A strong correlation was established between all POP serum levels and age. We established a positive relationship between high serum levels of βHCH and BMI and HOMAIR, whereas serum PCB levels were inversely correlated with BMI and HOMAIR. Combined, these results suggest that the diabetogenic effect of low‐dose exposure to POPs might be more complicated than a simple obesogenic effect. 相似文献