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831.
832.
Hellgren M Strömberg P Gallego O Martras S Farrés J Persson B Parés X Höög JO 《Cellular and molecular life sciences : CMLS》2007,64(4):498-505
The metabolism of all-trans- and 9-cis-retinol/ retinaldehyde has been investigated with focus on the activities of human, mouse and rat alcohol dehydrogenase 2
(ADH2), an intriguing enzyme with apparently different functions in human and rodents. Kinetic constants were determined with
an HPLC method and a structural approach was implemented by in silico substrate dockings. For human ADH2, the determined Km values ranged from 0.05 to 0.3 μM and kcat values from 2.3 to 17.6 min−1, while the catalytic efficiency for 9-cis-retinol showed the highest value for any substrate. In contrast, poor activities
were detected for the rodent enzymes. A mouse ADH2 mutant (ADH2Pro47His) was studied that resembles the human ADH2 setup.
This mutation increased the retinoid activity up to 100-fold. The Km values of human ADH2 are the lowest among all known human retinol dehydrogenases, which clearly support a role in hepatic
retinol oxidation at physiological concentrations.
Received 12 October 2006; received after revision 6 December 2006; accepted 8 January 2007 相似文献
833.
Untangling the molecular nature of sperm-egg interactions is fundamental if we are to understand fertilization. These phenomena
have been studied for many years using biochemical approaches such as antibodies and ligands that interact with sperm or with
eggs and their vestments. However, when homologous genetic recombination techniques were applied, most of the phenotypic factors
of the gene-manipulated animals believed “essential” for fertilization were found to be dispensable. Of course, all biological
systems contain redundancies and compensatory mechanisms, but as a whole the old model of fertilization clearly requires significant
modification. In this review, we use the results of gene manipulation experiments in animals to propose the basis for a new
vision.
Received 26 January 2007; received after revision 7 March 2007; accepted 17 April 2007 相似文献
834.
Minagawa H Yoshida Y Kenmochi N Furuichi M Shimada J Kaneko H 《Cellular and molecular life sciences : CMLS》2007,64(1):77-81
Lactate oxidase is used in biosensors to measure the concentration of lactate in the blood and other body fluids. Increasing
the thermostability of lactate oxidase can significantly prolong the lifetime of these biosensors. We have previously obtained
a variant of lactate oxidase from Aerococcus viridans with two mutations (E160G/V198I) that is significantly more thermostable than the wild-type enzyme. Here we have attempted
to further improve the thermostability of E160G/V198I lactate oxidase using directed evolution. We made a mutant lactate oxidase
gene library by applying error-prone PCR and DNA shuffling, and screened for thermostable mutant lactate oxidase using a plate-based
assay. After three rounds of screening we obtained a thermostable mutant lactate oxidase, which has six mutations (E160G/V198I/G36S/T103S/A232S/F277Y).
The half-life of this lactate oxidase at 70 °C was about 2 times that of E160G/V198I and about 36 times that of the wild-type
enzyme. The amino acid mutation process suggests that the combined neutral mutations are important in protein evolution.
Received 15 September 2006; received after revision 21 October 2006; accepted 2 November 2006 相似文献
835.
Crnković-Mertens I Wagener N Semzow J Gröne EF Haferkamp A Hohenfellner M Butz K Hoppe-Seyler F 《Cellular and molecular life sciences : CMLS》2007,64(9):1137-1144
Cancer cells are typically characterized by apoptosis deficiency. In order to investigate a possible role for the anti-apoptotic
livin gene in renal cell cancer (RCC), we analyzed its expression in tumor tissue samples and in RCC-derived cell lines. In addition,
we studied the contribution of livin to the apoptotic resistance of RCC cells by RNA interference (RNAi). Livin gene expression was detected in a significant portion of RCC tumor tissue specimens (13/14, 92.9%) and tumor-derived cell
lines (12/15, 80.0%). Moreover, targeted inhibition of livin by RNAi markedly sensitized RCC cells towards proapoptotic stimuli, such as UV irradiation or the chemotherapeutic drugs
etoposide, 5-fluorouracil, and vinblastine. These effects were specific for livin expressing tumor cells. We conclude that livin can contribute significantly to the apoptosis resistance of RCC cells. Targeted inhibition of livin could represent a novel therapeutic strategy to increase the sensitivity of renal cancers towards pro-apoptotic agents.
Received 30 November 2006; received after revision 22 February 2007; accepted 20 March 2007 相似文献
836.
837.
Larrucea S Butta N Rodriguez RB Alonso-Martin S Arias-Salgado EG Ayuso MS Parrilla R 《Cellular and molecular life sciences : CMLS》2007,64(22):2965-2974
Podocalyxin (PODXL) is a mucin protein of the CD34 family expressed in kidney glomerular podocytes, vascular endothelium,
progenitor bone marrow and tumor cells. It is assumed that PODXL plays an anti-adherent role in kidney podocytes. CHO cells
stably expressing human PODXL (CHO-PODXL) or human tumor cells (Tera-1) inherently expressing PODXL showed increased adherence
to platelets. The adherence of cells was inhibited (70%) by blockers of platelet P-selectin, prevented by the soluble ectodomain
of human PODXL (PODXL-Δ) or by the arginine-glycine-aspartate (RGDS) peptide and partially impeded by inhibition of integrin
αVβ3/αVβ5, suggesting a coordinated action of P-selectin and integrins. Colocalization of platelet P-selectin and PODXL expressed
on CHO cells was demonstrated by confocal immunofluorescence. No adherence to platelets was observed when PODXL was expressed
in glycomutant CHO cells deficient in sialic acid.
Received 14 August 2007; received after revision 12 September 2007; accepted 13 September 2007 相似文献
838.
Dreschers S Dumitru CA Adams C Gulbins E 《Cellular and molecular life sciences : CMLS》2007,64(2):181-191
Rhinoviruses, which cause common cold, belong to the Picornaviridae family, small non-enveloped viruses (diameter 15-30 nm) containing a single-stranded RNA genome (about 7 kb). Over 100 different rhinoviral serotypes have been identified thus far, establishing rhinoviruses as the most diverse group of Picornaviridae. Based on receptor binding properties, rhinoviruses are divided into two classes: the major group binding to intracellular adhesion molecule-1 and the minor group binding to the very low density lipoprotein receptors. Interactions between virus and the receptor molecules cause a conformational change in the capsid, which is a prerequisite for viral uptake. Rhinoviruses trigger a chemokine response upon infection that may lead to exacerbation of the symptoms of common cold, i.e. asthma and inflammation. The following review aims to summarize the knowledge about rhinoviral infections and discusses therapeutical approaches against this almost perfectly adapted pathogen. 相似文献
839.
Receptor communication within the lymphocyte plasma membrane: a role for the thrombospondin family of matricellular proteins 总被引:1,自引:0,他引:1
Lymphocytes, the principal cells of the immune system, carry out immune surveillance throughout the body by their unique capacity
to constantly reposition themselves between a free-floating vascular state and a tissue state characterized by migration and
frequent adhesive interactions with endothelial cells and components of the extracellular matrix. Therefore, mechanisms co-ordinating
adhesion and migration with signals delivered through antigen recognition probably play a pivotal role for the regulation
of lymphocyte behaviour and function. Endogenous thrombospondin-1 (TSP-1) seems to be the hub in such a mechanism for autocrine
regulation of T cell adhesion and migration. TSP-1 functions as a mediator of cis interaction of vital receptors within the T lymphocyte plasma membrane, including integrins, low density lipoprotein receptor-related
protein, calreticulin and integrin-associated protein.
Received 1 June 2006; received after revision 28 June 2006; accepted 11 October 2006 相似文献
840.
From old organisms to new molecules: integrative biology and therapeutic targets in accelerated human ageing 总被引:6,自引:1,他引:5
Understanding the basic biology of human ageing is a key milestone in attempting to ameliorate the deleterious consequences of old age. This is an urgent research priority given the global demographic shift towards an ageing population. Although some molecular pathways that have been proposed to contribute to ageing have been discovered using classical biochemistry and genetics, the complex, polygenic and stochastic nature of ageing is such that the process as a whole is not immediately amenable to biochemical analysis. Thus, attempts have been made to elucidate the causes of monogenic progeroid disorders that recapitulate some, if not all, features of normal ageing in the hope that this may contribute to our understanding of normal human ageing. Two canonical progeroid disorders are Werner's syndrome and Hutchinson-Gilford progeroid syndrome (also known as progeria). Because such disorders are essentially phenocopies of ageing, rather than ageing itself, advances made in understanding their pathogenesis must always be contextualised within theories proposed to help explain how the normal process operates. One such possible ageing mechanism is described by the cell senescence hypothesis of ageing. Here, we discuss this hypothesis and demonstrate that it provides a plausible explanation for many of the ageing phenotypes seen in Werner's syndrome and Hutchinson-Gilford progeriod syndrome. The recent exciting advances made in potential therapies for these two syndromes are also reviewed. 相似文献