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181.
Taylor DM Maxwell MM Luthi-Carter R Kazantsev AG 《Cellular and molecular life sciences : CMLS》2008,65(24):4000-4018
Sirtuins comprise a unique class of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that target multiple protein substrates to execute diverse biological functions. These enzymes are
key regulators of clinically important cellular and organismal processes, including metabolism, cell division and aging. The
desire to understand the important determinants of human health and lifespan has resulted in a firestorm of work on the seven
mammalian sirtuins in less than a decade. The implication of sirtuins in medically important areas such as diabetes, cancer,
cardiovascular dysfunction and neurodegenerative disease has further catapulted them to a prominent status as potential targets
for nutritional and therapeutic development. Here, we present a review of published results on sirtuin biology and its relevance
to human disease.
Received 25 June 2008; received after revision 20 August 2008; accepted 29 August 2008 相似文献
182.
Papaconstantinou ME Gandhi PS Chen Z Bah A Di Cera E 《Cellular and molecular life sciences : CMLS》2008,65(22):3688-3697
Meizothrombin is the physiologically active intermediate generated by a single cleavage of prothrombin at R320 to separate the A and B chains. Recent evidence has suggested that meizothrombin, like thrombin, is a Na(+)-activated enzyme. In this study we present the first X-ray crystal structure of human meizothrombin desF1 solved in the presence of the active site inhibitor PPACK at 2.1 A resolution. The structure reveals a Na(+) binding site whose architecture is practically identical to that of human thrombin. Stopped-flow measurements of Na(+) binding to meizothrombin desF1 document a slow phase of fluorescence change with a k(obs) decreasing hyperbolically with increasing [Na(+)], consistent with the existence of three conformations in equilibrium, E*, E and E:Na(+), as for human thrombin. Evidence that meizothrombin exists in multiple conformations provides valuable new information for studies of the mechanism of prothrombin activation. 相似文献
183.
Zinc binding to peptide analogs of the structural zinc site in alcohol dehydrogenase: Implications for an entatic state 总被引:1,自引:0,他引:1
Bergman T Zhang K Palmberg C Jörnvall H Auld DS 《Cellular and molecular life sciences : CMLS》2008,65(24):4019-4027
Zinc binding to the peptide replica and analogs to residues 93–115 of horse liver alcohol dehydrogenase (ADH) was examined
by competition of the peptides and the chromophoric chelator 4-(2- pyridylazo)resorcinol for zinc and X-ray absorption fine
structure analysis of the zinc ligands. In the enzyme, zinc is coordinated by four Cys residues. In the peptide replica, zinc
is bound to three Cys and one His residue. A four-Cys zinc coordination is observed only when His is removed, leading to increased
zinc stability. ADH crystal structures reveal that the ε-amino group of the conserved residue Lys323 is within H-bond distance
of the backbone amide oxygens of residues 103, 105 and 108, likely stabilizing the zinc coordination in the enzyme. The peptide
data thus indicate structural strain and increased energy in the zinc-binding site in the protein, characteristic of an entatic
state, implying a functional nature for this zinc site.
Received 3 July 2008; received after revision 11 August 2008; accepted 1 September 2008 相似文献
184.
Muñoz U Bartolomé F Esteras N Bermejo-Pareja F Martín-Requero A 《Cellular and molecular life sciences : CMLS》2008,65(21):3507-3519
It has been proposed that neuroinflammation, among other factors, may trigger an aberrant neuronal cell cycle re-entry leading
to neuronal death. Cell cycle disturbances are also detectable in peripheral cells from Alzheimer’s disease (AD) patients.
We previously reported that the anti-inflammatory 15- deoxy-Δ12,14-prostaglandin J
2 (15d-PGJ
2) increased the cellular content of the cyclin-dependent kinase inhibitor p27, in lymphoblasts from AD patients. This work
aimed at elucidating the mechanisms of 15d-PGJ
2-induced p27 accumulation. Phosphorylation, half-life, and the nucleo-cytoplasmic traffic of p27 protein were altered by 15d-PGJ2
by mechanisms dependent on PI3K/Akt activity. 15d-PGJ
2 prevents the calmodulin-dependent Akt overactivation in AD lymphoblasts by blocking its binding to the 85-kDa regulatory
subunit of PI3K. These effects of 15d-PGJ
2 were not mimicked by 9,10-dihydro-15-deoxy-Δ12,14- prostaglandin J
2, suggesting that 15d-PGJ
2 acts independently of peroxisome proliferator-activated receptor γ activation and that the α,β-unsaturated carbonyl group
in the cyclopentenone ring of 15d-PGJ
2 is a requisite for the observed effects.
Received 14 July 2008; received after revision 2 September 2008; accepted 12 September 2008 相似文献
185.
Molecular mechanisms of phagocytic uptake in mammalian cells 总被引:2,自引:1,他引:1
Groves E Dart AE Covarelli V Caron E 《Cellular and molecular life sciences : CMLS》2008,65(13):1957-1976
Phagocytosis is a highly conserved, complex process that has evolved to counter the constant threat posed by pathogens, effete cells and debris. Classically defined as a mechanism for internalising and destroying particles greater than 0.5 mum in size, it is a receptor-mediated, actin-driven process. The best-studied phagocytic receptors are the opsono-receptors, FcgammaR and CR3. Phagocytic uptake involves actin dynamics including polymerisation, bundling, contraction, severing and depolymerisation of actin filaments. Recent evidence points to the importance of membrane remodelling during phagocytosis, both in terms of changes in lipid composition and delivery of new membrane to the sites of particle binding. Here we review the molecular mechanisms of phagocytic uptake and some of the strategies developed by microbial pathogens to manipulate this process. 相似文献
186.
Cardiolipin, the heart of mitochondrial metabolism 总被引:5,自引:0,他引:5
Cardiolipin is a unique phospholipid, which is almost exclusively localized in the mitochondrial inner membrane where it is
synthesized from phosphatidylglycerol and cytidinediphosphate-diacylglycerol. After primary synthesis, the mature acyl chain
composition of cardiolipin is achieved by at least two remodeling mechanisms. In the mitochondrial membrane cardiolipin plays
an important role in energy metabolism, mainly by providing stability for the individual enzymes and enzyme complexes involved
in energy production. Moreover, cardiolipin is involved in different stages of the mitochondrial apoptotic process and in
mitochondrial membrane dynamics. Cardiolipin alterations have been described in various pathological conditions. Patients
suffering from Barth syndrome have an altered cardiolipin homeostasis caused by a primary deficiency in cardiolipin remodeling.
Alterations in cardiolipin content or composition have also been reported in more frequent diseases such as diabetes and heart
failure. In this review we provide an overview of cardiolipin metabolism, function and its role in different pathological
states.
Received 16 January 2008; received after revision 26 February 2008; accepted 26 March 2008 相似文献
187.
Galat A 《Cellular and molecular life sciences : CMLS》2008,65(21):3481-3493
Extracellular domains of some cellular receptors expressed in the organisms at different levels of development belong to three-fingered
protein (TFP) fold. The Homo sapiens genome encodes at least 45 genes containing from one to three TFP domains (TFPDs), namely diverse paralogues of the Ly6 gene,
CD59 and the receptors of activins, bone morphogenetic proteins, Mullerian inhibiting substance and transforming growth factor-β.
C4.4a and urokinase/plasminogen activatory receptor contain two and three TFPD repeats, respectively. These diverse proteins
have a low overall sequence similarity with each other and their hydrophobicity levels vary to a considerable degree. It is
suggested that sequence differentiation within the TFPD led to distinct groups of proteins whose attributes were optimized
to fit both the physicochemical properties specific to their functional microenvironment and selective targeting of their
highly diversified extracellular cofactors.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 7 August 2008; accepted 29 August 2008 相似文献
188.
全语言教育理念及对我国幼儿园语言教育的启示 总被引:4,自引:0,他引:4
马雪琴 《大庆师范学院学报》2012,(1):140-142
全语言教育是近年来学前教育界比较重要的一种新的语言教育理念。全语言教育强调儿童的语言学习是整体性的学习,是在真实世界中进行的有效的和有用的学习,是开放而平等的学习,是与其他领域的学习融合在一起的学习。全语言教育理念对我国当前幼儿园语言教育教学改革有积极的推动作用,并有如下启示:幼儿园语言教育应该是完整的、全面的,幼儿语言教育活动的过程应是真实的,幼儿园语言教育应采用多样化的形式开展,幼儿园语言教育应与其他领域的活动相整合。 相似文献
189.
190.
The macromolecular peptide-loading complex in MHC class I-dependent antigen presentation 总被引:5,自引:1,他引:4
A challenging task for the adaptive immune system of vertebrates is to identify and eliminate intracellular antigens. Therefore
a highly specialized antigen presentation machinery has evolved to display fragments of newly synthesized proteins to effector
cells of the immune system at the cell surface. After proteasomal degradation of unwanted proteins or defective ribosome products,
resulting peptides are translocated into the endoplasmic reticulum by the transporter associated with antigen processing and
loaded onto major histocompatibility complex (MHC) class I molecules. Peptide-MHC I complexes are transported via the secretory
pathway to the cell surface where they are then inspected by cytotoxic T lymphocytes, which can trigger an immune response.
This review summarizes the current view of the intracellular machinery of antigen processing and of viral immune escape mechanisms
to circumvent destruction by the host.
Received 4 October 2005; received after revision 19 November 2005; accepted 24 November 2005 相似文献