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81.
Christoph Heier Ulrike Taschler Maja Radulovic Philip Aschauer Thomas O. Eichmann Susanne Grond Heimo Wolinski Monika Oberer Rudolf Zechner Sepp D. Kohlwein Robert Zimmermann 《The Journal of biological chemistry》2016,291(22):11865-11875
Fatty acid ethyl esters (FAEEs) are non-oxidative metabolites of ethanol that accumulate in human tissues upon ethanol intake. Although FAEEs are considered as toxic metabolites causing cellular dysfunction and tissue damage, the enzymology of FAEE metabolism remains poorly understood. In this study, we used a biochemical screen in Saccharomyces cerevisiae to identify and characterize putative hydrolases involved in FAEE catabolism. We found that Yju3p, the functional orthologue of mammalian monoacylglycerol lipase (MGL), contributes >90% of cellular FAEE hydrolase activity, and its loss leads to the accumulation of FAEE. Heterologous expression of mammalian MGL in yju3Δ mutants restored cellular FAEE hydrolase activity and FAEE catabolism. Moreover, overexpression or pharmacological inhibition of MGL in mouse AML-12 hepatocytes decreased or increased FAEE levels, respectively. FAEEs were transiently incorporated into lipid droplets (LDs) and both Yju3p and MGL co-localized with these organelles. We conclude that the storage of FAEE in inert LDs and their mobilization by LD-resident FAEE hydrolases facilitate a controlled metabolism of these potentially toxic lipid metabolites. 相似文献
82.
Harry Kolles Winfried Förderer Rudolf Bock Wolfgang Feiden 《Histochemistry and cell biology》1993,100(4):293-296
In this note we present a combined Ki-67 and Feulgen stain for morphometric determination of the Ki-67 labelling index. The immunohistochemical part of this double staining technique is based on the alkaline-phosphatase-anti-alkaline-phosphatase (APAAP) method, visualizing the enzyme activity by the nitro-blue-tetrazolium chloride (NBT)/bromo-chloro-3-indolyl-phosphate (BCIP) technique. The NBT/BCIP complex resists the hydrolytic activity of the Feulgen stain. The staining method presented allows semi-automatic determination of both the total nucleus-area as well as the Ki-67 positive nucleus-area using a morphometric computer system. The Ki-67 labelling index thus achieved is based on the relative nuclear area of Ki-67 positive nuclei and is clearly more precise and efficient than the counting method using an ocular grid. 相似文献
83.
Hennecke G Nolte J Volkmer-Engert R Schneider-Mergener J Behrens S 《The Journal of biological chemistry》2005,280(25):23540-23548
The Escherichia coli periplasmic chaperone and peptidyl-prolyl isomerase (PPIase) SurA facilitates the maturation of outer membrane porins. Although the PPIase activity exhibited by one of its two parvulin-like domains is dispensable for this function, the chaperone activity residing in the non-PPIase regions of SurA, a sizable N-terminal domain and a short C-terminal tail, is essential. Unlike most cytoplasmic chaperones SurA is selective for particular substrates and recognizes outer membrane porins synthesized in vitro much more efficiently than other proteins. Thus, SurA may be specialized for the maturation of outer membrane proteins. We have characterized the substrate specificity of SurA based on its natural, biologically relevant substrates by screening cellulose-bound peptide libraries representing outer membrane proteins. We show that two features are critical for peptide binding by SurA: specific patterns of aromatic residues and the orientation of their side chains, which are found more frequently in integral outer membrane proteins than in other proteins. For the first time this sufficiently explains the capability of SurA to discriminate between outer membrane protein and non-outer membrane protein folding intermediates. Furthermore, peptide binding by SurA requires neither an active PPIase domain nor the presence of proline, indicating that the observed substrate specificity relates to the chaperone function of SurA. Finally, we show that SurA is capable of associating with the outer membrane. Together, our data support a model in which SurA is specialized to interact with non-native periplasmic outer membrane protein folding intermediates and to assist in their maturation from early to late outer membrane-associated steps. 相似文献
84.
Christos E. Zois Anne M. Hendriks Syed Haider Elisabete Pires Esther Bridges Dimitra Kalamida Dimitrios Voukantsis B. Christoffer Lagerholm Rudolf S. N. Fehrmann Wilfred F. A. den Dunnen Andrei I. Tarasov Otto Baba John Morris Francesca M. Buffa James S. O. McCullagh Mathilde Jalving Adrian L. Harris 《Cell death & disease》2022,13(6)
Channelling of glucose via glycogen, known as the glycogen shunt, may play an important role in the metabolism of brain tumours, especially in hypoxic conditions. We aimed to dissect the role of glycogen degradation in glioblastoma (GBM) response to ionising radiation (IR). Knockdown of the glycogen phosphorylase liver isoform (PYGL), but not the brain isoform (PYGB), decreased clonogenic growth and survival of GBM cell lines and sensitised them to IR doses of 10–12 Gy. Two to five days after IR exposure of PYGL knockdown GBM cells, mitotic catastrophy and a giant multinucleated cell morphology with senescence-like phenotype developed. The basal levels of the lysosomal enzyme alpha-acid glucosidase (GAA), essential for autolysosomal glycogen degradation, and the lipidated forms of gamma-aminobutyric acid receptor-associated protein-like (GABARAPL1 and GABARAPL2) increased in shPYGL U87MG cells, suggesting a compensatory mechanism of glycogen degradation. In response to IR, dysregulation of autophagy was shown by accumulation of the p62 and the lipidated form of GABARAPL1 and GABARAPL2 in shPYGL U87MG cells. IR increased the mitochondrial mass and the colocalisation of mitochondria with lysosomes in shPYGL cells, thereby indicating reduced mitophagy. These changes coincided with increased phosphorylation of AMP-activated protein kinase and acetyl-CoA carboxylase 2, slower ATP generation in response to glucose loading and progressive loss of oxidative phosphorylation. The resulting metabolic deficiencies affected the availability of ATP required for mitosis, resulting in the mitotic catastrophy observed in shPYGL cells following IR. PYGL mRNA and protein levels were higher in human GBM than in normal human brain tissues and high PYGL mRNA expression in GBM correlated with poor patient survival. In conclusion, we show a major new role for glycogen metabolism in GBM cancer. Inhibition of glycogen degradation sensitises GBM cells to high-dose IR indicating that PYGL is a potential novel target for the treatment of GBMs.Subject terms: Cancer metabolism, CNS cancer 相似文献
85.
ULTRASTRUCTURAL CHANGES IN REGRESSING TAIL MUSCLES OF XENOPUS LARVAE AT METAMORPHOSIS 总被引:4,自引:3,他引:1 下载免费PDF全文
Rudolf Weber 《The Journal of cell biology》1964,22(2):481-487
86.
87.
Rudolf Fluri 《Archives of microbiology》1959,33(3):195-222
Ohne ZusammenfassungTeilergebnisse aus einer Inauguraldissertation der philosophisch-naturwissen-schaftlichen Fakultät der Universität Bern zur Erlangung der Doktorwürde 1958. 相似文献
88.
89.
Rudolf Ranninger 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1943,15(2):39-43
Ohne Zusammenfassung 相似文献
90.
Rudolf Freisleben 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1943,15(2):25-29
Zusammenfassung Es wird eine kultivierte Form vonHordeum agriocrithon ausLhasa (Tibet) beschrieben. Diese mehrzeilige, spindelbrüchige Kulturgerste wird mit der vonÅberg gefundenen, wahrscheinlich wilden, HerkunftTaofu verglichen. Die Bedeutung beider für die Evolution der Kulturgersten wird erörtert.Ergebnisse der Tibet-ExpeditionE. Schäfer 1938/39, Nr. 2. 相似文献