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1.
Kenis H Hofstra L Reutelingsperger CP 《Cellular and molecular life sciences : CMLS》2007,64(22):2859-2862
The surge in apoptosis research and the discovery of the phosphatidylserine binding properties of annexin A5 have propelled
a tremendous interest in cell death detection technologies. In the past years, annexin A5 has evolved from an efficient assay
for detection of apoptotic cells in vitro to an in vivo molecular imaging technology with potential clinical use. A second key discovery, the specific internalization properties
of annexin A5, has opened the opportunity to use annexin A5 for therapeutic applications. Annexin A5-mediated internalization
creates a novel therapeutic platform for targeted drug delivery and cell entry to treat various diseases, including cancer
and cardiovascular disease.
Received 29 June 2007; received after revision 19 July 2007; accepted 15 August 2007 相似文献
2.
The family of iron responsive RNA structures regulated by changes in cellular iron and oxygen 总被引:1,自引:1,他引:0
The life of aerobes is dependent on iron and oxygen for efficient bioenergetics. Due to potential risks associated with iron/oxygen
chemistry, iron acquisition, concentration, storage, utilization, and efflux are tightly regulated in the cell. A central
role in regulating iron/oxygen chemistry in animals is played by mRNA translation or turnover via the iron responsive element
(IRE)/iron regulatory protein (IRP) system. The IRE family is composed of three-dimensional RNA structures located in 3′ or
5′ untranslated regions of mRNA. To date, there are 11 different IRE mRNAs in the family, regulated through translation initiation
or mRNA stability. Iron or oxidant stimuli induce a set of graded responses related to mRNA-specific IRE substructures, indicated
by differential responses to iron in vivo and binding IRPs in vitro. Molecular effects of phosphorylation, iron and oxygen remain to be added to the structural information of the IRE-RNA and
IRP repressor in the regulatory complex.
Received 21 April 2007; received after revision 13 July 2007; accepted 2 August 2007 相似文献
3.
Polyphenolic phytochemicals are ubiquitous in plants, in which they function in various protective roles. A ‘recommended’
human diet contains significant quantities of polyphenolics, as they have long been assumed to be ‘antioxidants’ that scavenge
excessive, damaging, free radicals arising from normal metabolic processes. There is recent evidence that polyphenolics also
have ‘indirect’ antioxidant effects through induction of endogenous protective enzymes. There is also increasing evidence
for many potential benefits through polyphenolic-mediated regulation of cellular processes such as inflammation. Inductive
or signalling effects may occur at concentrations much lower than required for effective radical scavenging. Over the last
2 – 3 years, there have been many exciting new developments in the elucidation of the in vivo mechanisms of the health benefits of polyphenolics. We summarise the current knowledge of the intake, bio-availability and
metabolism of polyphenolics, their antioxidant effects, regulatory effects on signalling pathways, neuro-protective effects
and regulatory effects on energy metabolism and gut health.
Received 14 May 2007; received after revision 27 June 2007; accepted 24 July 2007 相似文献
4.
Hellgren M Kaiser C de Haij S Norberg A Höög JO 《Cellular and molecular life sciences : CMLS》2007,64(23):3129-3138
Subunit interaction in sorbitol dehydrogenase (SDH) has been studied with in vitro and in silico methods identifying a vital hydrogen-bonding network, which is strictly conserved among mammalian SDH proteins. Mutation
of one of the residues in the hydrogen-bonding network, Tyr110Phe, abolished the enzymatic activity and destabilized the protein
into tetramers, dimers and monomers as judged from gel filtration experiments at different temperatures compared to only tetramers
for the wild-type protein below 307 K. The determined equilibrium constants revealed a large difference in Gibbs energy (8
kJ/mol) for the tetramer stability between wild-type SDH and the mutated form Tyr110Phe SDH. The results focus on a network
of coupled hydrogen bonds in wild-type SDH that uphold the protein interface, which is specific and favorable to electrostatic,
van der Waals and hydrogen-bond interactions between subunits, interactions that are crucial for the catalytic power of SDH.
Received 13 July 2007; received after revision 30 September 2007; accepted 1 October 2007 相似文献
5.
S. Kjellev 《Cellular and molecular life sciences : CMLS》2009,66(8):1350-1369
The trefoil factor family (TFF) comprises a group of small peptides which are highly expressed in tissues containing mucus-producing
cells – especially in the mucosa lining the gastrointestinal tract. The peptides seem crucial for epithelial restitution and
may work via other pathways than the conventional factors involved in restitution. In vitro studies have shown that the TFFs promote restitution using multiple mechanisms. The peptides also have other functionalities
including interactions with the immune system. Moreover, therapeutic effects of the TFFs have been shown in several animal
models of gastrointestinal damage. Still it is not clear which of their in vitro properties are involved in the in vivo mode of action. This review describes the TFF family with emphasis on their biological properties and involvement in mucosal
protection and repair.
Received 10 October 2008; received after revision 07 November 2008; accepted 10 November 2008 相似文献
6.
Jedrzejas MJ 《Cellular and molecular life sciences : CMLS》2007,64(21):2799-2822
Bacteria present a variety of molecules either on their surface or in a cell-free form. These molecules take part in numerous
processes in the interactions with their host, with its tissues and other molecules. These molecules are essential to bacterial
pathogenesis either during colonization or the spread/invasion stages, and most are virulence factors. This review is focused
on such molecules using Streptococcus pneumoniae, a Gram-positive bacterium, as an example. Selected surface proteins are introduced, their structure described, and, whenever
available, their mechanisms of function on an atomic level are explained. Such mechanisms for hyaluronate lyase, pneumococcal
surface protein A, pneumolysin, histidine-triad and fibronectin-binding proteins are discussed. Elucidation of molecular mechanisms
of virulence factors is essential for the understanding of bacteria and their functional properties. Structural biology appears
pivotal for these studies, as structural and mechanistic insights facilitate rational approach to the development of new treatments.
Received 12 March 2007; received after revision 28 June 2007; accepted 18 July 2007 相似文献
7.
Bhavani S. Sahu Parshuram J. Sonawane Nitish R. Mahapatra 《Cellular and molecular life sciences : CMLS》2010,67(6):861-874
Chromogranin A (CHGA) is ubiquitously expressed in secretory cells of the endocrine, neuroendocrine, and neuronal tissues.
Although this protein has long been known as a marker for neuroendocrine tumors, its role in cardiovascular disease states
including essential hypertension (EH) has only recently been recognized. It acts as a prohormone giving rise to bioactive
peptides such as vasostatin-I (human CHGA1–76) and catestatin (human CHGA352–372) that exhibit several cardiovascular regulatory functions. CHGA is over-expressed but catestatin is diminished in EH. Moreover,
genetic variants in the promoter, catestatin, and 3′-untranslated regions of the human CHGA gene alter autonomic activity and blood pressure. Consistent with these findings, targeted ablation of this gene causes severe
arterial hypertension and ventricular hypertrophy in mice. Transgenic expression of the human CHGA gene or exogenous administration of catestatin restores blood pressure in these mice. Thus, the accumulated evidence establishes
CHGA as a novel susceptibility gene for EH. 相似文献
8.
Nutrigenomics has the potential to tailor diets to optimize health, based on knowledge of key genetic polymorphisms. Identification
of candidate genes is often based on a priori knowledge of disease processes. However, genome-wide association methods are not only validating previously identified genes
and polymorphisms, but also revealing new gene-disease associations not anticipated from prior knowledge. In Crohn’s disease
(CD), such studies not only confirm the importance of caspase-activated recruitment domain 15 and major histocompatability
complex II molecules, but also reveal strong associations with the proinflammatory cytokine interleukin-23 receptor and autophagy-related
16-like gene. Genes identified to date in CD can be linked into two interrelated pathways: receptor-mediated cytokine induction
or autophagocytosis. New genomic technologies need to be matched with innovative methodologies to characterize the likely
impact of foods and to take the field to another dimension of value for human diet development and optimized health.
Received 2 July 2007; received after revision 31 July 2007; accepted 29 August 2007 相似文献
9.
Tsatsanis C Dermitzaki E Venihaki M Chatzaki E Minas V Gravanis A Margioris AN 《Cellular and molecular life sciences : CMLS》2007,64(13):1638-1655
Corticotropin-releasing factor (CRF), also termed corticotropin-releasing hormone (CRH) or corticoliberin, is the major regulator
of the adaptive response to internal or external stresses. An essential component of the adaptation mechanism is the adrenal
gland. CRF regulates adrenal function indirectly through the central nervous system (CNS) via the hypothalamic-pituitary-adrenal
(HPA) axis and via the autonomic nervous system by way of locus coeruleus (LC) in the brain stem. Accumulating evidence suggests
that CRF and its related peptides also affect the adrenals directly, i.e. not through the CNS but from within the adrenal gland where they form paracrine regulatory loops. Indeed, CRF and its related
peptides, the urocortins (UCNs: UCN1, UCN2 and UCN3), their receptors CRF type 1 (CRF1) and 2 (CRF2) as well as the endogenous pseudo-receptor CRF-binding protein (CRF-BP) are all expressed in adrenal cortical, medullary
chromaffin and resident immune cells. The intra-adrenal CRF-based regulatory system is complex and depends on the balance
between the local concentration of CRF ligands and the availability of their receptors.
Received 19 December 2006; received after revision 20 February 2007; accepted 26 March 2007 相似文献
10.
Kertész A Váradi G Tóth GK Fajka-Boja R Monostori E Sármay G 《Cellular and molecular life sciences : CMLS》2006,63(22):2682-2693
Phosphopeptides interacting with src homology 2 (SH2) domains can activate essential signaling enzymes in vitro. When delivered to cells, they may disrupt protein-protein interactions, thereby influencing intracellular signaling. We
showed earlier that phosphopeptides corresponding to the inhibitory motif of Fcγ receptor IIb and a motif of the Grb2-associated
binder 1 adaptor protein activate SH2-containing tyrosine phosphatase 2 in vitro. To study the ex vivo effects of these peptides, we have now compared different methods for peptide delivery: (i) permeabilization of the target
cells and (ii) the use of cell-permeable vectors, which are potentially able to transport biologically active compounds into
B cells. We found octanoyl-Arg8 to be an optimal carrier for the delivery of phosphopeptides to the cells. With this strategy, the function of cell-permeable
SHP-2-binding phosphopeptides was analyzed. These peptides modulated the protein phosphorylation in B cells in a dose- and
time-dependent manner.
Received 27 July 2006; received after revision 4 September 2006; accepted 18 September 2006 相似文献
11.
The compositional difference in microbial and human cell membranes allows antimicrobial peptides to preferentially bind microbes.
Peptides which specifically target lipopolysaccharide (LPS) and palmitoyl-oleoyl-phosphatidylglycerol (POPG) are efficient
antibiotics. From the core LPS-binding region of Factor C, two 34-mer Sushi peptides, S1 and S3, were derived. S1 functions
as a monomer, while S3 is active as a dimer. Both S1 and S3 display detergent-like properties in disrupting LPS aggregates,
with specificity for POPG resulting from electrostatic and hydrophobic forces between the peptides and the bacterial lipids.
During interaction with POPG, the S1 transitioned from a random coil to an α-helix, while S3 resumed a mixture of α-helix
and β-sheet structures. The unsaturated nature of POPG confers fluidity and enhances insertion of the peptides into the lipid
bilayer, causing maximal disruption of the bacterial membrane. These parameters should be considered in designing and developing
new generations of peptide antibiotics with LPS-neutralizing capability.
Received 2 October 2007; received after revision 2 November 2007; accepted 4 December 2007
J. L. Ding, B. Ho: Co-senior authors. 相似文献
12.
Antisense transcription: A critical look in both directions 总被引:3,自引:1,他引:2
13.
In recent years the interest in antimicrobial proteins and peptides and their mode of action has been rapidly increasing due
to their potential to prevent and combat microbial infections in all areas of life. A detailed knowledge about the function
of such proteins is the most important requirement to consider them for future application. Our research in recent years has
been focused on the low molecular weight, cysteine-rich and cationic antifungal protein PAF from Penicillium chrysogenum, which inhibits the growth of opportunistic zoo-pathogens including Aspergillus fumigatus, numerous plant-pathogenic fungi and the model organism Aspergillus nidulans. So far, the experimental results indicate that PAF elicits hyperpolarization of the plasma membrane and the activation of
ion channels, followed by an increase in reactive oxygen species in the cell and the induction of an apoptosis-like phenotype.
Detailed knowledge about the molecular mechanism of action of antifungal proteins such as PAF contributes to the development
of new antimicrobial strategies that are urgently needed.
Received 09 August 2007; received after revision 17 September 2007; accepted 19 September 2007 相似文献
14.
The venoms of predatory cone snails (genus Conus) have yielded a complex library of about 50–100,000 bioactive peptides, each believed to have a specific physiological target
(although peptides from different species may overlap in their target specificity). Conus has evolved the equivalent of a drug development strategy that combines the accelerated evolution of toxin sequences with
an unprecedented degree of posttranslational modification. Some Conus venom peptide families are the most highly posttranslationally modified classes of gene products known. We review the variety
and complexity of posttranslational modifications documented in Conus peptides so far, and explore the potential of Conus venom peptides as a model system for a more general understanding of which secreted gene products may have modified amino
acids. Although the database of modified conotoxins is growing rapidly, there are far more questions raised than answers provided
about possible mechanisms and functions of posttranslational modifications in Conus.
Received 24 June 2005; received after revision 13 August 2005; accepted 19 September 2005 相似文献
15.
Investigations into mechanisms that restrict the recovery of functions after an injury to the brain or the spinal cord have
led to the discovery of specific neurite growth inhibitory factors in the adult central nervous system (CNS) of mammals. Blocking
their growth-suppressive function resulted in disinhibition of axonal growth, i.e. growth of cultured neurons on inhibitory
CNS tissue in vitro and regeneration of injured axons in vivo. The enhanced regenerative and compensatory fibre growth was often accompanied by a substantial improvement in the functional
recovery after CNS injury. The first clinical studies to assess the therapeutic potential of compounds that neutralize growth
inhibitors or interfere with their downstream signalling are currently in progress. This review discusses recent advances
in the understanding of how the ‘founder molecule’ Nogo-A and other glialderived growth inhibitors restrict the regeneration
and repair of disrupted neuronal circuits, thus limiting the functional recovery after CNS injuries.
Received 5 April 2007; received after revision 28 September 2007; accepted 1 October 2007 相似文献
16.
Silverman GA Whisstock JC Askew DJ Pak SC Luke CJ Cataltepe S Irving JA Bird PI 《Cellular and molecular life sciences : CMLS》2004,61(3):301-325
Serpins are unique among the various types of active site proteinase inhibitors because they covalently trap their targets by undergoing an irreversible conformational rearrangement. Members of the serpin superfamily are present in the three major domains of life (Bacteria, Archaea and Eukarya) as well as several eukaryotic viruses. The human genome encodes for at least 35 members that segregate evolutionarily into nine (A-I) distinct clades. Most of the human serpins are secreted and circulate in the bloodstream where they reside at critical checkpoints intersecting self-perpetuating proteolytic cascades such as those of the clotting, thrombolytic and complement systems. Unlike these circulating serpins, the clade B serpins (ov-serpins) lack signal peptides and reside primarily within cells. Most of the human clade B serpins inhibit serine and/or papain-like cysteine proteinases and protect cells from exogenous and endogenous proteinase-mediated injury. Moreover, as sequencing projects expand to the genomes of other species, it has become apparent that intracellular serpins belonging to distinct phylogenic clades are also present in the three major domains of life. As some of these serpins also guard cells against the deleterious effects of promiscuous proteolytic activity, we propose that this cytoprotective function, along with similarities in structure are common features of a cohort of intracellular serpin clades from a wide variety of species.Received 24 June 2003; received after revision 16 July 2003; accepted 5 August 2003 相似文献
17.
Lubelski J Rink R Khusainov R Moll GN Kuipers OP 《Cellular and molecular life sciences : CMLS》2008,65(3):455-476
This review discusses the state-of-the-art in molecular research on the most prominent and widely applied lantibiotic, i.e., nisin. The developments in understanding its complex biosynthesis and mode of action are highlighted. Moreover, novel applications
arising from engineering either nisin itself, or from the construction of totally novel dehydrated and/or lanthionine-containing
peptides with desired bioactivities are described. Several challenges still exist in understanding the immunity system and
the unique multiple reactions occurring on a single substrate molecule, carried out by the dehydratase NisB and the cyclization
enzyme NisC. The recent elucidation of the 3-D structure of NisC forms the exciting beginning of further 3-D-structure determinations
of the other biosynthetic enzymes, transporters and immunity proteins. Advances in achieving in vitro activities of lanthionine-forming enzymes will greatly enhance our understanding of the molecular characteristics of the
biosynthesis process, opening up new avenues for developing unique and novel biocatalytic processes.
Received 9 April 2007; received after revision 31 August 2007; accepted 28 September 2007 相似文献
18.
Polyembryonic development, where multiple embryos are formed from a single zygote, evolved at least 15 times in six different
phyla in animals. The mechanisms leading to polyembryony and the forces that shaped the evolution of the polyembryonic developmental
program have remained poorly understood. Recent studies of the polyembryonic development in the endoparasitic wasp Copidosoma floridanum have revealed that the evolution of polyembryony is associated with the evolution of developmental novelties such as total
cleavage, early specification of embryonic and extra-embryonic fates, and a specific cell proliferation phase. These changes
cumulatively result in the formation of thousands of embryos from a single egg. Laser ablation studies and analysis of early
cell fate specification have revealed that a single blastomere representing the progenitor of the primordial germ cell regulates
the proliferation of the embryos. We propose that evolutionary changes in cell cleavage, cell interactions, and the cell-differentiation
program, reminiscent of interactions between the germinal stem cell and stem cell niche in fly ovaries, underlies the evolution
of polyembryony.
Received 30 January 2007; received after revision 21 June 2007; accepted 11 July 2007 相似文献
19.
20.
Wittkopp PJ 《Cellular and molecular life sciences : CMLS》2005,62(16):1779-1783
Regulatory variation results from genetic changes with both cis and trans acting effects on gene expression. Here I describe the types of genetic variants that alter cis and trans regulation and discuss differences in the potential for cis and trans changes among different classes of genes. I argue that the molecular function of the protein encoded by each gene and how the gene is wired into the genomic regulatory network may influence its propensity for cis and trans regulatory changes.Received 15 February 2005; received after revision 12 April 2005; accepted 26 April 2005 相似文献