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41.
N-3 long chain polyunsaturated fatty acids: a nutritional tool to prevent insulin resistance associated to type 2 diabetes and obesity? 总被引:10,自引:0,他引:10
n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFA), mainly eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3), are present in mammal tissues both from endogenous synthesis from desaturation and elongation of 18:3 n-3 and/or from dietary origin (marine products and fish oils). In rodents in vivo, n-3 LC-PUFA have a protective effect against high fat diet induced insulin resistance. Such an effect is explained at the molecular level by the prevention of many alterations of insulin signaling induced by a high fat diet. Indeed, the protective effect of n-3 LC-PUFA results from the following: (a) the prevention of the decrease of phosphatidyl inositol 3' kinase (PI3 kinase) activity and of the depletion of the glucose transporter protein GLUT4 in the muscle; (b) the prevention of the decreased expression of GLUT4 in adipose tissue. In addition, n-3 LC-PUFA inhibit both the activity and expression of liver glucose-6-phosphatase which could explain the protective effect with respect to the excessive hepatic glucose output induced by a high fat diet. n-3 LC-PUFA also decrease muscle intramyofibrillar triglycerides and liver steatosis. This last effect results on the one hand, from a decreased expression of lipogenesis enzymes and of delta 9 desaturase (via a depleting effect on sterol response element binding protein 1c (SREBP-1c). On the other hand, n-3 LC-PUFA stimulate fatty acid oxidation in the liver (via the activation of peroxisome proliferator activated receptor alpha (PPAR-alpha)). In patients with type 2 diabetes, fish oil dietary supplementation fails to reverse insulin resistance for unclear reasons, but systematically decreases plasma triglycerides. Conversely, in healthy humans, fish oil has many physiological effects. Indeed, fish oil reduces insulin response to oral glucose without altering the glycaemic response, abolishes extraggression at times of mental stress, decreases the activation of sympathetic activity during mental stress and also decreases plasma triglycerides. These effects are encouraging in the perspective of prevention of insulin resistance but further clinical and basic studies must be designed to confirm and complete our knowledge in this field. 相似文献
42.
In silico screening of a saturated mutation library of tomato 总被引:4,自引:0,他引:4
Menda N Semel Y Peled D Eshed Y Zamir D 《The Plant journal : for cell and molecular biology》2004,38(5):861-872
A comprehensive mutant population is a basic resource for exploring gene function. We developed an isogenic tomato 'mutation library' in the genetic background of the inbred variety M82. A total of 13 000 M(2) families, derived from EMS (ethyl methane sulfonate) and fast-neutron mutagenesis, were visually phenotyped in the field and categorized into a morphological catalog that includes 15 primary and 48 secondary categories. Currently, 3417 mutations have been cataloged; among them are most of the previously described phenotypes from the monogenic mutant collection of The Tomato Genetics Resource Center, and over a thousand new mutants, with multiple alleles per locus. The phenotypic database indicates that most mutations fall into more than a single category (pleiotropic), with some organs such as leaves more prone to alterations than others. All data and images can be searched and accessed in the Solanaceae Genome Network (SGN) on a site called 'The Genes That Make Tomatoes' (http://zamir.sgn.cornell.edu/mutants/). 相似文献
43.
44.
A glycosylated type I membrane protein becomes cytosolic when peptide: N-glycanase is compromised 总被引:2,自引:0,他引:2
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The human cytomegalovirus-encoded glycoprotein US2 catalyzes proteasomal degradation of Class I major histocompatibility complex (MHC) heavy chains (HCs) through dislocation of the latter from the endoplasmic reticulum (ER) to the cytosol. During this process, the Class I MHC HCs are deglycosylated by an N-glycanase-type activity. siRNA molecules designed to inhibit the expression of the light chain, beta(2)-microglobulin, block the dislocation of Class I MHC molecules, which implies that US2-dependent dislocation utilizes correctly folded Class I MHC molecules as a substrate. Here we demonstrate it is peptide: N-glycanase (PNGase or PNG1) that deglycosylates dislocated Class I MHC HCs. Reduction of PNGase activity by siRNA expression in US2-expressing cells inhibits deglycosylation of Class I MHC HC molecules. In PNGase siRNA-treated cells, glycosylated HCs appear in the cytosol, providing the first evidence for the presence of an intact N-linked type I membrane glycoprotein in the cytosol. N-glycanase activity is therefore not required for dislocation of glycosylated Class I MHC molecules from the ER. 相似文献
45.
Methionine sulfoxide reductases protect Ffh from oxidative damages in Escherichia coli 总被引:1,自引:0,他引:1
In proteins, methionine residues are primary targets for oxidation. Methionine oxidation is reversed by methionine sulfoxide reductases A and B, a class of highly conserved enzymes. Ffh protein, a component of the ubiquitous signal recognition particle, contains a methionine-rich domain, interacting with a small 4.5S RNA. In vitro analyses reported here show that: (i) oxidized Ffh is unable to bind 4.5S RNA, (ii) oxidized Ffh contains methionine sulfoxide residues, (iii) oxidized Ffh is a substrate for MsrA and MsrB enzymes; and (iv) MsrA/B repairing activities allow oxidized Ffh to recover 4.5S RNA-binding abilities. In vivo analyses reveal that: (i) Ffh synthesized in the msrA msrB mutant contains methionine sulfoxide residues and is unstable, (ii) msrA msrB mutant requires high levels of Ffh synthesis for growth and (iii) msrA msrB mutation leads to defects in Ffh-dependent targeting of MalF. We conclude that MsrA and MsrB are required to repair Ffh oxidized by reactive oxygen species produced by aerobic metabolism, establishing an as-yet undescribed link between protein targeting and oxidation. 相似文献
46.
To investigate how the complex organization of heterochromatin is reproduced at each replication cycle, we examined the fate of HP1-rich pericentric domains in mouse cells. We find that replication occurs mainly at the surface of these domains where both PCNA and chromatin assembly factor 1 (CAF-1) are located. Pulse-chase experiments combined with high-resolution analysis and 3D modeling show that within 90 min newly replicated DNA become internalized inside the domain. Remarkably, during this time period, a specific subset of HP1 molecules (alpha and gamma) coinciding with CAF-1 and replicative sites is resistant to RNase treatment. Furthermore, these replication-associated HP1 molecules are detected in Suv39 knockout cells, which otherwise lack stable HP1 staining at pericentric heterochromatin. This replicative pool of HP1 molecules disappears completely following p150CAF-1 siRNA treatment. We conclude that during replication, the interaction of HP1 with p150CAF-1 is essential to promote delivery of HP1 molecules to heterochromatic sites, where they are subsequently retained by further interactions with methylated H3-K9 and RNA. 相似文献
47.
The helicoidal organization of secondary cell walls is overviewed from several examples. Both the plywood texture and the occurrence of characteristic defects strongly suggest that the wall ordering is relevant of a cholesteric liquid-crystal assembly that is rapidly and strongly consolidated by lignification. A preferential localization of glucuronoxylans, major matrix components, and in vitro re-association experiments emphasize their preeminent role: (1) during the construction of the composite as directing the cellulose microfibrils in a helicoidal array; (2) during the lignification of the composite as a host structure for lignin precursors. 相似文献
48.
Biological systems excel at building spatial structures on scales ranging from nanometers to kilometers and exhibit temporal patterning from milliseconds to years. One approach that nature has taken to accomplish this relies on the harnessing of pattern-forming processes of non-equilibrium physics and chemistry. For these systems, the study of biological pattern formation starts with placing a biological phenomenon of interest within the context of the proper pattern-formation schema and then focusing on the ways in which control is exerted to adapt the pattern to the needs of the organism. This approach is illustrated by several examples, notably bacterial colonies (diffusive-growth schema) and intracellular calcium waves (excitable-media schema). 相似文献
49.
Antibacterial and proteolytic activity in venom from the endoparasitic wasp Pimpla hypochondriaca (Hymenoptera: Ichneumonidae) 总被引:3,自引:0,他引:3
Venom from the endoparasitic wasp, Pimpla hypochondriaca, is composed of a mixture of high and low molecular weight proteins, possesses phenoloxidase activity, has immunosuppressive properties, and induces paralysis in several insect species. In the present study we demonstrate that P. hypochondriaca venom also contains antibacterial and proteolytic activity. Antibacterial activity was detected against the Gram-negative bacteria Escherichia coli and Xanthamonas campestris but not against Pseudomonas syringae nor against two Gram-positive bacteria, Bacillus cereus and Bacillus subtilis. Endopeptidase and aminopeptidase activity in venom was detected using the synthetic fluorogenic substrates N-t-BOC-Phe-Ser-Arg-AMC, Arg-AMC and Leu-Arg. The aminopeptidase activity towards Arg-AMC was sensitive to amastatin (70% inhibition), an aminopeptidase inhibitor. Angiotensin-converting enzyme (ACE)-like enzyme activity was detected, by reverse-phase HPLC using the synthetic tripeptide Hip-His-Leu as a substrate. This activity was sensitive to captopril, an ACE inhibitor (IC(50) 3.8 x 10(-8) M). Using an antiserum raised against recombinant Drosophila melanogaster ACE-like enzyme, (rAnce), Western blot analysis revealed an immunoreactive protein, with a molecular weight estimate of 74 kDa, in P. hypochondriaca venom. The possibility that the endopeptidase, aminopeptidase and ACE are involved in the processing of peptide precursors in the venom sac is discussed. 相似文献
50.
Prolonged culture in low glucose induces apoptosis of rat pancreatic beta-cells through induction of c-myc 总被引:4,自引:0,他引:4
Van de Casteele M Kefas BA Cai Y Heimberg H Scott DK Henquin JC Pipeleers D Jonas JC 《Biochemical and biophysical research communications》2003,312(4):937-944
Prolonged culture in low-glucose concentrations (=5mM) induces apoptosis in pancreatic beta-cells by a poorly defined mechanism. We now show that, in both purified rat beta-cells and isolated rat islets, culture in the presence of 3 or 5mM (G3-G5) instead of 10mM glucose (G10) induces a large increase in c-myc expression before onset of a caspase-dependent apoptosis. These effects were prevented by addition of leucine and glutamine to G3 and G5, and were mimicked by addition of the mitochondrial poison azide to G10. In contrast, inhibition of Ca(2+) influx and insulin secretion with diazoxide under control conditions did not stimulate islet c-myc expression nor beta-cell apoptosis. In rat beta-cells, adenovirus-mediated c-myc overexpression increased their rate of apoptosis, whereas antisense-c-myc expression reduced low-glucose-induced apoptosis by approximately 50%. In the insulin producing MIN6 cell line, apoptosis induction by either low glucose or an activator of AMP-activated protein kinase (AMPK) was associated with c-myc mRNA and protein upregulation. In conclusion, stimulation of beta-cell apoptosis by prolonged culture at low glucose partly results from early and sustained induction of beta-cell c-myc expression. These effects may be due to sustained restriction in nutrient-derived metabolic signals. 相似文献