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61.
An alternative method for serum protein depletion/enrichment by precipitation at mildly acidic pH values and low ionic strength 下载免费PDF全文
Ann‐Kristin Henning Dirk Albrecht Katharina Riedel Thomas C. Mettenleiter Axel Karger 《Proteomics》2015,15(11):1935-1940
Serum proteome analysis is severely hampered by the extreme dynamic range of protein concentrations, but tools for the specific depletion of highly abundant serum proteins lack for most farm and companion animals. A well‐established alternative strategy to reduce the dynamic range of plasma protein concentrations, treatment with combinatorial peptide ligand libraries (CPLL), is generally applicable but requires large amounts of sample. Therefore, additional depletion/enrichment protocols for plasma and serum samples from animals are desirable. In this respect, we have tested a protein precipitate that formed after withdrawal of salt from human, bovine, or porcine serum at pH 4.2. The bovine sample was composed of over 300 proteins making it a potential source for biomarker discovery. Precipitation was highly reproducible and the concentrations of albumin and other highly abundant serum proteins were strongly reduced. In comparison to the CPLL treatment, precipitation did not introduce any selection bias based on hydrophathy or pI. However, the composition of both preparations was partially complementary. Salt withdrawal at pH 4.2 is suggested as additional depletion/enrichment strategy for serum samples. Also, we point out that the removal of precipitates from serum samples under the described conditions bears the risk of losing a valuable protein fraction. 相似文献
62.
Identification of cathepsin B as a mediator of neuronal death induced by Abeta-activated microglial cells using a functional genomics approach 总被引:5,自引:0,他引:5
63.
Ruey-Jane?Fan Antonia?Marin-Burgin Kathleen?A.?French W.?Otto FriesenEmail author 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2005,191(12):1157-1171
Although the neuronal circuits that generate leech movements have been studied for over 30 years, the list of interneurons
(INs) in these circuits remains incomplete. Previous studies showed that some motor neurons (MNs) are electrically coupled
to swim-related INs, e.g., rectifying junctions connect IN 28 to MN DI-1 (dorsal inhibitor), so we searched for additional
neurons in these behavioral circuits by co-injecting Neurobiotin and Alexa Fluor 488 into segmental MNs DI–1, VI–2, DE–3 and
VE–4. The high molecular weight Alexa dye is confined to the injected cell, whereas the smaller Neurobiotin molecules diffuse
through gap junctions to reveal electrical coupling. We found that MNs were each dye-coupled to approximately 25 neurons,
about half of which are likely to be INs. We also found that (1) dye-coupling was reliably correlated with physiologically
confirmed electrical connections, (2) dye-coupling is unidirectional between MNs that are linked by rectifying connections,
and (3) there are novel electrical connections between excitatory and inhibitory MNs, e.g. between excitatory MN VE-4 and
inhibitory MN DI-1. The INs found in this study provide a pool of novel candidate neurons for future studies of behavioral
circuits, including those underlying swimming, crawling, shortening, and bending movements. 相似文献
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Jan Terje Andersen Bj?rn Dalhus Dorthe Viuff Birgitte Thue Ravn Kristin St?en Gunnarsen Andrew Plumridge Karen Bunting Filipa Antunes Rebecca Williamson Steven Athwal Elizabeth Allan Leslie Evans Magnar Bj?r?s S?ren Kj?rulff Darrell Sleep Inger Sandlie Jason Cameron 《The Journal of biological chemistry》2014,289(19):13492-13502
A major challenge for the therapeutic use of many peptides and proteins is their short circulatory half-life. Albumin has an extended serum half-life of 3 weeks because of its size and FcRn-mediated recycling that prevents intracellular degradation, properties shared with IgG antibodies. Engineering the strictly pH-dependent IgG-FcRn interaction is known to extend IgG half-life. However, this principle has not been extensively explored for albumin. We have engineered human albumin by introducing single point mutations in the C-terminal end that generated a panel of variants with greatly improved affinities for FcRn. One variant (K573P) with 12-fold improved affinity showed extended serum half-life in normal mice, mice transgenic for human FcRn, and cynomolgus monkeys. Importantly, favorable binding to FcRn was maintained when a single-chain fragment variable antibody was genetically fused to either the N- or the C-terminal end. The engineered albumin variants may be attractive for improving the serum half-life of biopharmaceuticals. 相似文献
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Pearl Quijada Nirmala Hariharan Jonathan D. Cubillo Kristin M. Bala Jacqueline M. Emathinger Bingyan J. Wang Lucia Ormachea Donald M. Bers Mark A. Sussman Coralie Poizat 《The Journal of biological chemistry》2015,290(42):25411-25426
Ca2+/Calmodulin-dependent protein kinase II (CaMKII) signaling in the heart regulates cardiomyocyte contractility and growth in response to elevated intracellular Ca2+. The δB isoform of CaMKII is the predominant nuclear splice variant in the adult heart and regulates cardiomyocyte hypertrophic gene expression by signaling to the histone deacetylase HDAC4. However, the role of CaMKIIδ in cardiac progenitor cells (CPCs) has not been previously explored. During post-natal growth endogenous CPCs display primarily cytosolic CaMKIIδ, which localizes to the nuclear compartment of CPCs after myocardial infarction injury. CPCs undergoing early differentiation in vitro increase levels of CaMKIIδB in the nuclear compartment where the kinase may contribute to the regulation of CPC commitment. CPCs modified with lentiviral-based constructs to overexpress CaMKIIδB (CPCeδB) have reduced proliferative rate compared with CPCs expressing eGFP alone (CPCe). Additionally, stable expression of CaMKIIδB promotes distinct morphological changes such as increased cell surface area and length of cells compared with CPCe. CPCeδB are resistant to oxidative stress induced by hydrogen peroxide (H2O2) relative to CPCe, whereas knockdown of CaMKIIδB resulted in an up-regulation of cell death and cellular senescence markers compared with scrambled treated controls. Dexamethasone (Dex) treatment increased mRNA and protein expression of cardiomyogenic markers cardiac troponin T and α-smooth muscle actin in CPCeδB compared with CPCe, suggesting increased differentiation. Therefore, CaMKIIδB may serve as a novel modulatory protein to enhance CPC survival and commitment into the cardiac and smooth muscle lineages. 相似文献
69.
A. D. Baxter A. H. Baillie M. M. Ferguson G. P. Lewis 《Histochemistry and cell biology》1966,7(3):218-223
Summary In these experiments, a considerable range of hydroxysteroid dehydrogenases were demonstrated in vertebrate hepatic tissue; 3, 3, 6, 11, 16, 16, 17 and 20 were consistently present.3 hydroxysteroid dehydrogenase was fairly active in mammalian liver, but consistently greater activity was seen with the 3 dehydrogenases which are probably concerned with steroid detoxication and excretion. 6 and 11 hydroxysteroids were only moderately well used, and both these were noticeably better used in male tissue, as were also 3, 3, 16 and 16 hydroxysteroids. All mammalian liver utilised 16, 16 and 17 compounds fairly well, and 20 was consistently but poorly used.This histochemical evidence agrees with biochemical and clinical evidence for the significance and nature of steroid metabolism in the liver. Many of the enzymes showing activity in the liver have known function in the detoxication and elimination of steroids; and 3-hydroxysteroid dehydrogenase is concerned in cholesterol biosynthesis as well as the biosynthesis of progesterane. To have shown contrasting patterns of activity between liver and steroid producing endocrine tissues is further evidence for the specificity of these techniques in the study of dehydrogenase distribution. 相似文献
70.
Munshi HG Ghosh S Mukhopadhyay S Wu YI Sen R Green KJ Stack MS 《The Journal of biological chemistry》2002,277(41):38159-38167
The expression and activity of epithelial proteinases is under stringent control to prevent aberrant hydrolysis of structural proteins and disruption of tissue architecture. E-cadherin-dependent cell-cell adhesion is also important for maintenance of epithelial structural integrity, and loss of E-cadherin expression has been correlated with enhanced invasive potential in multiple tumor models. To address the hypothesis that there is a functional link between E-cadherin and proteinase expression, we have examined the role of E-cadherin in proteinase regulation. By using a calcium switch protocol to manipulate junction assembly, our data demonstrate that initiation of de novo E-cadherin-mediated adhesive contacts suppresses expression of both relative matrix metalloproteinase-9 levels and net urinary-type plasminogen activator activity. E-cadherin-mediated cell-cell adhesion increases both phosphatidylinositol 3'-kinase (PI3-kinase)-dependent AKT phosphorylation and epidermal growth factor receptor-dependent MAPK/ERK activation. Pharmacologic inhibition of the PI3-kinase pathway, but not the epidermal growth factor receptor/MAPK pathway, prevents E-cadherin-mediated suppression of proteinases and delays junction assembly. Moreover, inhibition of junction assembly with a function-blocking anti-E-cadherin antibody stimulates proteinase-dependent Matrigel invasion. As matrix metalloproteinase-9 and urinary-type plasminogen activator potentiate the invasive activity of oral squamous cell carcinoma, these data suggest E-cadherin-mediated signaling through PI3-kinase can regulate the invasive behavior of cells by modulating proteinase secretion. 相似文献