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101.
102.
Akt activity negatively regulates phosphorylation of AMP-activated protein kinase in the heart 总被引:10,自引:0,他引:10
Kovacic S Soltys CL Barr AJ Shiojima I Walsh K Dyck JR 《The Journal of biological chemistry》2003,278(41):39422-39427
In the heart, insulin stimulates a variety of kinase cascades and controls glucose utilization. Because insulin is able to activate Akt and inactivate AMP-activated protein kinase (AMPK) in the heart, we hypothesized that Akt can regulate the activity of AMPK. To address the potential existence of this novel signaling pathway, we used a number of experimental protocols to activate Akt in cardiac myocytes and monitored the activation status of AMPK. Mouse hearts perfused in the presence of insulin demonstrated accelerated glycolysis and glucose oxidation rates as compared with non-insulin-perfused hearts. In addition, insulin caused an increase in Akt phosphorylation and a decrease in AMPK phosphorylation at its major regulatory site (threonine 172 of the alpha catalytic subunit). Transgenic mice overexpressing a constitutively active mutant form of Akt1 displayed decreased phosphorylation of cardiac alpha-AMPK. Isolated neonatal cardiac myocytes infected with an adenovirus expressing constitutively active mutant forms of either Akt1 or Akt2 also suppressed AMPK phosphorylation. However, Akt-dependent depression of alpha-AMPK phosphorylation could be overcome in the presence of the AMPK activator, metformin, suggesting that an override mechanism exists that can restore AMPK activity. Taken together, this study suggests that there is cross-talk between the AMPK and Akt pathways and that Akt activation can lead to decreased AMPK activity. In addition, our data suggest that the ability of insulin to inhibit AMPK may be controlled via an Akt-mediated mechanism. 相似文献
103.
Sánchez-Mendoza M. Ortigoza-Ferado J. Barrón-Romero B.L. Mota-de-la-Garza L. 《World journal of microbiology & biotechnology》2001,17(2):211-213
MAb anti-Staphylococcal enterotoxins (MAb-SE) were produced in mice with a mixture of reference SE types A, B, C1 and D at a concentration of 1 g each per mouse; the last booster injection was by intrasplenic route. Nine clones were chosen, two produced anti-SEB and anti-SED, one anti-SEA and anti-SEB, two anti-SED, two anti-SEB and one produced anti-SEC1. The MAb-SE were partially purified as judged by PAGE–SDS. The partially purified antibodies could demonstrate the presence of SE in milk samples containing 0.5 g of toxin m l–1. 相似文献
104.
105.
Altier C Dubel SJ Barrère C Jarvis SE Stotz SC Spaetgens RL Scott JD Cornet V De Waard M Zamponi GW Nargeot J Bourinet E 《The Journal of biological chemistry》2002,277(37):33598-33603
Accurate calcium signaling requires spatial and temporal coordination of voltage-gated calcium channels (VGCCs) and a variety of signal transduction proteins. Accordingly, regulation of L-type VGCCs involves the assembly of complexes that include the channel subunits, protein kinase A (PKA), protein kinase A anchoring proteins (AKAPs), and beta2-adrenergic receptors, although the molecular details underlying these interactions remain enigmatic. We show here, by combining extracellular epitope splicing into the channel pore-forming subunit and immunoassays with whole cell and single channel electrophysiological recordings, that AKAP79 directly regulates cell surface expression of L-type calcium channels independently of PKA. This regulation involves a short polyproline sequence contained specifically within the II-III cytoplasmic loop of the channel. Thus we propose a novel mechanism whereby AKAP79 and L-type VGCCs function as components of a biosynthetic mechanism that favors membrane incorporation of organized molecular complexes in a manner that is independent of PKA phosphorylation events. 相似文献
106.
Iron (Fe) chlorosis is common in olive (Olea europaea L.) trees growing on highly calcareous soils in Southern Spain, where generally causes reduction in yield, size and commercial value of the olives. The objective of this research was to study the effectiveness of synthetic vivianite (Fe3(PO4)2H2O) to reduce Fe chlorosis in olive. Experiments were established in three orchards with cultivars `Hojiblanco', `Manzanillo', and `Picual'. The design was a randomised block design with two or three treatments (control with no Fe fertiliser and vivianite at one or two rates). A vivianite suspension (0.05 kg dm–3 water) was injected into the soil at 10–20 points around the tree at the depth of maximum root density (25–35 cm). The rates (and times of application) were 0.5 and 1 kg tree–1 for `Hojiblanco' (March 1997), 1 kg tree–1 for `Manzanillo' (March 1998), and 2 kg tree–1 for `Picual' (March 1998). The leaf chlorophyll content index (CCI) was estimated on the youngest expanded leaves by means of a Minolta apparatus (SPAD units). The colour index of the olives was estimated by visual comparison with a scale ranging from 1 (pale yellow) to 8 (normal green). For the period studied (July 1997–November 1999), the CCI of fertilised trees was, in general, significantly higher than that of control trees, and so was the case with the olive colour index. Olive yield, measured in the experimental fields with `Hojiblanco' (in 1999) and `Manzanillo' (in 1998 and 1999), was higher for the fertilised than for the control trees but differences were only significant in 1999. These results suggest that vivianite is effective to reduce Fe chlorosis for more than two seasons. Such effectiveness is probably due to the poorly crystalline Fe(III) oxides (which are good sources of Fe to plants) that result from the slow oxidation and incongruent dissolution of vivianite. 相似文献
107.
Barr FA 《Current opinion in cell biology》2002,14(4):496-499
Yeast and mammalian cells use a variety of different mechanisms to ensure that the endoplasmic reticulum and Golgi apparatus are inherited by both daughter cells on cell division. In yeast, endoplasmic reticulum inheritance involves both active microtubule and passive actin-based mechanisms, while the Golgi is transported into the forming daughter cell by an active actin-based mechanism. Animal cells actively partition the endoplasmic reticulum and Golgi apparatus, but association with the mitotic spindle-rather than the actin cytoskeleton-appears to be the mechanism 相似文献
108.
Inestrosa N De Ferrari GV Garrido JL Alvarez A Olivares GH Barría MI Bronfman M Chacón MA 《Neurochemistry international》2002,41(5):341-344
Alzheimer's disease (AD) is a progressive dementia paralleled by selective neuronal death, which is probably caused by the cytotoxic effects of the amyloid-beta peptide (Abeta). We have observed that Abeta-dependent neurotoxicity induces a loss of function of Wnt signaling components and that activation of this signaling cascade prevent such cytotoxic effects. Therefore we propose that compounds which mimic this signaling cascade may be candidates for therapeutic intervention in Alzheimer's patients. 相似文献
109.
110.
Hervé F d'Athis P Tremblay D Tillement JP Barré J 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2003,798(2):283-294
Human alpha1-acid glycoprotein (AAG) is a mixture of at least two genetic variants, the A variant and the F1 and/or S variant or variants, which are encoded by two different genes. AAG is also an extensively glycosylated protein which possesses five N-linked glycans exhibiting substantial heterogeneity in their structures. The first objective of this study was to investigate the glycosylation of the two major gene products of AAG, i.e. the A variant and a mixture of the F1 and S variants (F1*S). To this end, we combined a chromatographic method for the fractionation of the AAG variants with a lectin-binding assay to characterise the glycosylation of purified glycoproteins. Secondly, because the oligosaccharides can influence the disposition of AAG, a kinetic study of the AAG variants was carried out in the rat. After intravenous administration of whole human AAG, the separation and quantification of the AAG variants in plasma was performed by application of specific methods by isoelectric focusing and immunonephelometry. The binding studies carried out on a panel of lectins showed significant differences in the lectin-binding characteristics of the separated F1*S and A variants, accounting for differences in the degree of branching of their glycan chains and substitution with sialic acid and fucose. The plasma concentration-time profiles of the F1*S and A variants were biphasic, and only small differences were observed between the variants for their initial and terminal half-lives, clearance and distribution volume. This indicates that the structural differences between the two AAG gene products do not affect their pharmacokinetics in the rat. Specific drug transport roles have been previously demonstrated for the F1*S and A variants, calling for further investigations into their effects on the disposition of drugs they bind in plasma. The present study shows that such investigations are possible without being complicated by kinetic differences between these variants. 相似文献