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71.
Terhi Vihervaara Riikka-Liisa Uronen Gerd Wohlfahrt Ingemar Björkhem Elina Ikonen Vesa M. Olkkonen 《Cellular and molecular life sciences : CMLS》2011,68(3):537-551
ORP1L is an oxysterol binding homologue that regulates late endosome (LE) positioning. We show that ORP1L binds several oxysterols
and cholesterol, and characterize a mutant, ORP1L Δ560–563, defective in oxysterol binding. While wild-type ORP1L clusters
LE, ORP1L Δ560–563 induces LE scattering, which is reversed by disruption of the endoplasmic reticulum (ER) targeting FFAT
motif, suggesting that it is due to enhanced LE–ER interactions. Endosome motility is reduced upon overexpression of ORP1L.
Both wild-type ORP1L and the Δ560–563 mutant induce the recruitment of both dynactin and kinesin-2 on LE. Most of the LE decorated
by overexpressed ORP1L fail to accept endocytosed dextran or EGF, and the transfected cells display defective degradation
of internalized EGF. ORP1L silencing in macrophage foam cells enhances endosome motility and results in inhibition of [3H]cholesterol efflux to apolipoprotein A-I. These data demonstrate that LE motility and functions in both protein and lipid
transport are regulated by ORP1L. 相似文献
72.
73.
J. v. Schönfeld M. Rünzi H. Goebell M. K. Müller 《Cellular and molecular life sciences : CMLS》1995,51(6):556-560
It is well known that oral administration of camostate induces hyperplasia and hypertrophy of the rat pancreas. It is not clear, however, whether pancreatic hormone and enzyme secretion are affected by camostate treatment.In rats, daily administration of 200 mg camostate/kg b. wt for 14 days significantly increased pancreatic weight and pancreatic content of DNA, protein, amylase, lipase, trypsin and chymotrypsin, as well as the amount of insulin, glucagon and somatostatin. In the intact animal, blood glucose levels and serum concentrations of insulin and glucagon in response to an oral glucose load were not impaired after camostate treatment. In the isolated perfused pancreas, however, insulin and glucagon secretions were reduced, whereas somatostatin release was not affected. The volume of pancreatic juice produced by the unstimulated isolated perfused organ, as well as protein and enzyme secretion, were increased after camostate treatment. Likewise, the isolated perfused pancreas from camostate-treated rats secreted a larger volume of pancreatic juice and more protein in response to cholecystokinin (CCK), while enzyme secretion was affected in a non-parallel manner: amylase release was markedly reduced, lipase release was unchanged, and release of trypsin and chymotrypsin was increased. 相似文献
74.
Leers MP Björklund V Björklund B Jörnvall H Nap M 《Cellular and molecular life sciences : CMLS》2002,59(8):1358-1365
We investigated the distribution and fate of apoptotic bodies during human development and in the adult, using an antibody
(M30) that recognizes a neo-epitope formed early in the apoptotic cascade by caspase cleavage of cytokeratin 18. In the fetus,
we found extensive accumulation of M30-positive, non-phagocytosed fragments in the red pulp of the spleen, subcutaneous and
submucosal vessels, the interstitium of the lung, and the glomerular mesangium of the kidneys. In the liver, M30-immunoreactive
fragments were found inside macrophages in the sinusoids. The number of these fragments and the intensity of the immunostaining
increased with the gestational age of the fetus. In the adult, M30-positive fragments were barely detectable in normal tissues.
However, many pathological situations, including both chronic degenerative processes and metastatic cancer, were associated
with accumulation of M30-positive fragments in the red pulp of the spleen. In the liver and kidney, no fragments could be
detected. Remarkably, 13 of the 16 patients with metastasized cancer showed pronounced accumulation of M30-positive fragments
containing hematoxylin-reactive material in the red pulp of the spleen. In the non-cancerous cases, such DNA-containing fragments
were only seen in 9 of 94 cases. The results show that when apoptotic activity is high, as during development in the fetus
or during metastasis and other pathological processes in the adult, the phagocytic clearance of apoptotic bodies can be overloaded.
These apoptotic fragments then accumulate in the spleen. The visual detection of apoptotic fragments is concluded to reflect
increased cell turnover.
Received 1 July 2002; accepted 1 July 2002 相似文献
75.
Strömberg P Svensson S Hedberg JJ Nordling E Höög JO 《Cellular and molecular life sciences : CMLS》2002,59(3):552-559
The human alcohol dehydrogenase system is comprised of multiple forms that catalyse the oxidation/reduction of a large variety of alcohols and aldehydes. A transition that results in an Ile308Val substitution was identified in the human ADH2 gene by single-strand conformation polymorphism analysis. Screening a Swedish population revealed that Val308 was the most frequent allele (73%), and site-directed mutagenesis was used to obtain both allelozymes, which were expressed in Escherichia coli for characterisation. Thermostability was assayed by activity measurements and circular dichroism spectroscopy. The results showed that the 308Val substitution decreases protein stability, as compared to the Ile308 variant, an effect also demonstrated during prolonged storage. Ethanol, octanol, 12-hydroxydodecanoic acid and all-trans retinol were used as model substrates and, generally, slightly higher Km values were observed with Val at position 308. Finally, homology modelling, from mouse ADH2, further supported the decreased stability of the Val308 variant and located position 308 in the subunit interface of the molecule and in the vicinity of the active-site pocket entrance. In conclusion, the Ile308Val substitution represents a novel functional polymorphism within the human alcohol dehydrogenase gene cluster that may affect the metabolism of ethanol and other substrates. 相似文献
76.
Wabnitz H Bittner L de Castro AR Döhrmann R Gürtler P Laarmann T Laasch W Schulz J Swiderski A von Haeften K Möller T Faatz B Fateev A Feldhaus J Gerth C Hahn U Saldin E Schneidmiller E Sytchev K Tiedtke K Treusch R Yurkov M 《Nature》2002,420(6915):482-485
Intense radiation from lasers has opened up many new areas of research in physics and chemistry, and has revolutionized optical technology. So far, most work in the field of nonlinear processes has been restricted to infrared, visible and ultraviolet light, although progress in the development of X-ray lasers has been made recently. With the advent of a free-electron laser in the soft-X-ray regime below 100 nm wavelength, a new light source is now available for experiments with intense, short-wavelength radiation that could be used to obtain deeper insights into the structure of matter. Other free-electron sources with even shorter wavelengths are planned for the future. Here we present initial results from a study of the interaction of soft X-ray radiation, generated by a free-electron laser, with Xe atoms and clusters. We find that, whereas Xe atoms become only singly ionized by the absorption of single photons, absorption in clusters is strongly enhanced. On average, each atom in large clusters absorbs up to 400 eV, corresponding to 30 photons. We suggest that the clusters are heated up and electrons are emitted after acquiring sufficient energy. The clusters finally disintegrate completely by Coulomb explosion. 相似文献
77.
Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs 总被引:6,自引:0,他引:6
Okazaki Y Furuno M Kasukawa T Adachi J Bono H Kondo S Nikaido I Osato N Saito R Suzuki H Yamanaka I Kiyosawa H Yagi K Tomaru Y Hasegawa Y Nogami A Schönbach C Gojobori T Baldarelli R Hill DP Bult C Hume DA Quackenbush J Schriml LM Kanapin A Matsuda H Batalov S Beisel KW Blake JA Bradt D Brusic V Chothia C Corbani LE Cousins S Dalla E Dragani TA Fletcher CF Forrest A Frazer KS Gaasterland T Gariboldi M Gissi C Godzik A Gough J Grimmond S Gustincich S Hirokawa N Jackson IJ Jarvis ED Kanai A 《Nature》2002,420(6915):563-573
78.
79.
Epithelial antimicrobial peptides: innate local host response elements 总被引:23,自引:0,他引:23
Schröder JM 《Cellular and molecular life sciences : CMLS》1999,56(1-2):32-46
Multicellular organisms have to survive in an environment laden with numerous microorganisms, which represent a potential hazard to life. Different strategies have been developed to ward off infections by preventing microorganisms from entering surfaces and by preventing the attack of microorganisms that have already entered the epithelia. Therefore, it is not surprising that epithelia are equipped with various antimicrobial substances that act rapidly to kill a broad range of microorganisms. This review summarizes our present knowledge about epithelial peptide antibiotics produced in plants, invertebrates, and vertebrates including humans. There is now strong evidence that in addition to constitutively secreted peptide antibiotics, others are induced upon contact with microorganisms or by proinflammatory cytokines. beta-Defensins represent one family of vertebrate antimicrobial peptides, members of which are inducible and have recently been identified in humans. The defensin-characteristic local expression pattern may indicate that specialized surfaces express a characteristic surface antimicrobial peptide pattern that might define the characteristic microflora as well as the density of microorganisms present on the surface. 相似文献
80.
Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1 总被引:8,自引:0,他引:8
Aminoff M Carter JE Chadwick RB Johnson C Gräsbeck R Abdelaal MA Broch H Jenner LB Verroust PJ Moestrup SK de la Chapelle A Krahe R 《Nature genetics》1999,21(3):309-313
Megaloblastic anaemia 1 (MGA1, OMIM 261100) is a rare, autosomal recessive disorder characterized by juvenile megaloblastic anaemia, as well as neurological symptoms that may be the only manifestations. At the cellular level, MGA1 is characterized by selective intestinal vitamin B12 (B12, cobalamin) malabsorption. MGA1 occurs worldwide, but its prevalence is higher in several Middle Eastern countries and Norway, and highest in Finland (0.8/100,000). We previously mapped the MGA1 locus by linkage analysis in Finnish and Norwegian families to a 6-cM region on chromosome 10p12.1 (ref. 8). A functional candidate gene encoding the intrinsic factor (IF)-B12 receptor, cubilin, was recently cloned; the human homologue, CUBN, was mapped to the same region. We have now refined the MGA1 region by linkage disequilibrium (LD) mapping, fine-mapped CUBN and identified two independent disease-specific CUBN mutations in 17 Finnish MGA1 families. Our genetic and molecular data indicate that mutations in CUBN cause MGA1. 相似文献