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Liem DA te Lintel Hekkert M Manintveld OC Boomsma F Verdouw PD Duncker DJ 《American journal of physiology. Heart and circulatory physiology》2005,288(3):H1165-H1172
Clinical studies on cardioprotection by preinfarct angina are ambiguous, which may involve development of tolerance to repeated episodes of ischemia. Not all preconditioning stimuli use identical signaling pathways, and because patients likely experience varying numbers of episodes of preinfarct angina of different degrees and durations, it is important to know whether myocardium tolerant to a particular preconditioning stimulus can still be protected by stimuli employing alternative signaling pathways. We tested the hypothesis that development of tolerance to a particular stimulus does not affect cardioprotection by stimuli that employ different signaling pathways. Anesthetized rats underwent classical, remote or pharmacological preconditioning. Infarct size (IS), produced by a 60-min coronary artery occlusion (CAO), was determined after 120 min of reperfusion. Preconditioning by two 15-min periods of CAO (2CAO15, an adenosine-dependent stimulus) limited IS from 69 +/- 2% to 37 +/- 6%, but when 2CAO15 was preceded by 4CAO15, protection by 2CAO15 was absent (IS = 68 +/- 1%). This development of tolerance coincided with a loss of cardiac interstitial adenosine release, whereas two 15-min infusions of adenosine (200 microg/min i.v.) still elicited cardioprotection (IS = 40 +/- 4%). Furthermore, cardioprotection was produced when 4CAO15 was followed by the adenosine-independent stimulus 3CAO3 (IS = 50 +/- 8%) or the remote preconditioning stimulus of two 15-min periods of mesenteric artery occlusion (IS = 49 +/- 6%). In conclusion, development of tolerance to cardioprotection by an adenosine-dependent preconditioning stimulus still allows protection by pharmacological or ischemic stimuli intervention employing different signaling pathways. 相似文献
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Malcolm Anastasius Celine Luquain-Costaz Maaike Kockx Wendy Jessup Leonard Kritharides 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2018,1863(10):1257-1273
The ‘cholesterol efflux capacity (CEC)’ assay is a simple in vitro measure of the capacities of individual sera to promote the first step of the reverse cholesterol transport pathway, the delivery of cellular cholesterol to plasma HDL.This review describes the cell biology of this model and critically assesses its application as a marker of cardiovascular risk. We describe the pathways for cell cholesterol export, current cell models used in the CEC assay with their limitations and consider the contribution that measurement of serum CEC provides to our understanding of HDL function in vivo. 相似文献
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Md. Qumruzzaman Chowdhury Peter Kitin Maaike De Ridder Claire Delvaux Hans Beeckman 《Trees - Structure and Function》2016,30(1):227-239
Key message
Cambial marking experiment and cambial activity analysis offer strong evidence on existence of annual growth rings in Heritiera fomes and revealing the potential of dendrochronological applications in Bangladesh mangroves.Abstract
Despite enormous significance in coastal protection, biodiversity conservation and livelihood support to the local communities, mangrove ecosystems have been continuously degrading mainly due to anthropogenic disturbances and climate change. Time series based on dated tree ring is an option to identify the causes of forest dilapidation. In this study, we investigated the structure and periodicity of the growth ring in Heritiera fomes, the flagship tree species of the Bangladesh Sundarbans, combining cambial marking experiment and cambial activity analysis. Distinct growth rings were found which are delineated by a band of marginal parenchyma, predominantly one cell wide but up to three and occasionally interrupted with fiber. Of the 13 trees with cambium marking experiment, one growth ring was found in each tree during a year. The dormant cambium was characterized by the abrupt boundary between xylem and cambial zone, absence of enlarging or differentiating cambial derivatives, lower number of cambial cells and thicker radial walls in cambial cells. Growth ring anomalies, i.e., wedging and partially missing rings were also found. In most of the cases, the lower part of the eccentric discs had low radial increment (<0.75 mm) and therefore the growth ring in that area merged with previous one and produced wedging or partially missing ring. However, the existence of annual rings suggests its great potential for future dendrochronological applications to reveal the dynamics of vegetation and climate in Sundarbans.114.
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Michiel van Gent Steven G. E. Braem Annemieke de Jong Nezira Delagic Janneke G. C. Peeters Ingrid G. J. Boer Paul N. Moynagh Elisabeth Kremmer Emmanuel J. Wiertz Huib Ovaa Bryan D. Griffin Maaike E. Ressing 《PLoS pathogens》2014,10(2)
Viral infection triggers an early host response through activation of pattern recognition receptors, including Toll-like receptors (TLR). TLR signaling cascades induce production of type I interferons and proinflammatory cytokines involved in establishing an anti-viral state as well as in orchestrating ensuing adaptive immunity. To allow infection, replication, and persistence, (herpes)viruses employ ingenious strategies to evade host immunity. The human gamma-herpesvirus Epstein-Barr virus (EBV) is a large, enveloped DNA virus persistently carried by more than 90% of adults worldwide. It is the causative agent of infectious mononucleosis and is associated with several malignant tumors. EBV activates TLRs, including TLR2, TLR3, and TLR9. Interestingly, both the expression of and signaling by TLRs is attenuated during productive EBV infection. Ubiquitination plays an important role in regulating TLR signaling and is controlled by ubiquitin ligases and deubiquitinases (DUBs). The EBV genome encodes three proteins reported to exert in vitro deubiquitinase activity. Using active site-directed probes, we show that one of these putative DUBs, the conserved herpesvirus large tegument protein BPLF1, acts as a functional DUB in EBV-producing B cells. The BPLF1 enzyme is expressed during the late phase of lytic EBV infection and is incorporated into viral particles. The N-terminal part of the large BPLF1 protein contains the catalytic site for DUB activity and suppresses TLR-mediated activation of NF-κB at, or downstream of, the TRAF6 signaling intermediate. A catalytically inactive mutant of this EBV protein did not reduce NF-κB activation, indicating that DUB activity is essential for attenuating TLR signal transduction. Our combined results show that EBV employs deubiquitination of signaling intermediates in the TLR cascade as a mechanism to counteract innate anti-viral immunity of infected hosts. 相似文献
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A Cell-penetrating Peptide Derived from Human Lactoferrin with Conformation-dependent Uptake Efficiency 总被引:1,自引:0,他引:1
Falk Duchardt Ivo R. Ruttekolk Wouter P. R. Verdurmen Hugues Lortat-Jacob Jochen Bürck Hansj?rg Hufnagel Rainer Fischer Maaike van den Heuvel Dennis W. P. M. L?wik Geerten W. Vuister Anne Ulrich Michel de Waard Roland Brock 《The Journal of biological chemistry》2009,284(52):36099-36108
The molecular events that contribute to the cellular uptake of cell-penetrating peptides (CPP) are still a matter of intense research. Here, we report on the identification and characterization of a 22-amino acid CPP derived from the human milk protein, lactoferrin. The peptide exhibits a conformation-dependent uptake efficiency that is correlated with efficient binding to heparan sulfate and lipid-induced conformational changes. The peptide contains a disulfide bridge formed by terminal cysteine residues. At concentrations exceeding 10 μm, this peptide undergoes the same rapid entry into the cytoplasm that was described previously for the arginine-rich CPPs nona-arginine and Tat. Cytoplasmic entry strictly depends on the presence of the disulfide bridge. To better understand this conformation dependence, NMR spectroscopy was performed for the free peptide, and CD measurements were performed for free and lipid-bound peptide. In solution, the peptides showed only slight differences in secondary structure, with a predominantly disordered structure both in the presence and absence of the disulfide bridge. In contrast, in complex with large unilamellar vesicles, the conformation of the oxidized and reduced forms of the peptide clearly differed. Moreover, surface plasmon resonance experiments showed that the oxidized form binds to heparan sulfate with a considerably higher affinity than the reduced form. Consistently, membrane binding and cellular uptake of the peptide were reduced when heparan sulfate chains were removed. 相似文献