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Jessica L. Slack Corey P. Causey Paul R. Thompson 《Cellular and molecular life sciences : CMLS》2011,68(4):709-720
The recent approvals of anticancer therapeutic agents targeting the histone deacetylases and DNA methyltransferases have highlighted
the important role that epigenetics plays in human diseases, and suggested that the factors controlling gene expression are
novel drug targets. Protein arginine deiminase 4 (PAD4) is one such target because its effects on gene expression parallel
those observed for the histone deacetylases. We demonstrated that F- and Cl-amidine, two potent PAD4 inhibitors, display micromolar
cytotoxic effects towards several cancerous cell lines (HL-60, MCF7 and HT-29); no effect was observed in noncancerous lines
(NIH 3T3 and HL-60 granulocytes). These compounds also induced the differentiation of HL-60 and HT29 cells. Finally, these
compounds synergistically potentiated the cell killing effects of doxorubicin. Taken together, these findings suggest PAD4
inhibition as a novel epigenetic approach for the treatment of cancer, and suggest that F- and Cl-amidine are candidate therapeutic
agents for this disease. 相似文献
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J. Portugal Alvarez C. Perezagua Clamagirand J. M. Arévalo Alonso A. Velasco Martín 《Cellular and molecular life sciences : CMLS》1972,28(12):1453-1454
Resumen Los fumadores habituales tienen niveles de FFA significantivamente más altos que los no fumadores. El acto de fumar incrementa la lipolisis. Fumar sin inhalar el humo produce incremento de lipolisis. La insulina inhibe la accion lipolítica del humo de tabaco. 相似文献
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Computer simulations at the atomic level have arrived at a stage where they provide realistic modeling of flexibility in proteins
(and the mobility of their associated solvent) that is important in understanding the nature of molecular motions. This can
now be extended to the molecular and atomic motions that are associated with protein mechanisms. Moreover, the derived data
agree reasonably accurately with experimental measurements of several kinetic and thermodynamic parameters. Fundamental insights
emerge on the roles that this intrinsic flexibility plays in the thermodynamic characteristics of macromolecules in solution;
these equip the investigator to probe the consequences of cognate interactions and ligand binding on entropy and enthalpy.
Thus simulations can now provide a powerful tool for investigating protein mechanisms that complements the existing and the
emerging experimental techniques.
Received 29 May 2005; received after revision 23 August 2005; accepted 21 October 2005 相似文献
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Antigenic activity of lobster (Homarus vulgaris) arginine kinase and its cyanogen bromide fragments]
Y Benyamin Y Robin F Regnouf 《Comptes rendus des séances de l'Académie des sciences. Série D, Sciences naturelles》1977,284(19):1955-1958
The antigenic saturation of lobster arginine kinase (38 000 daltons) by its specific antibodies has been studied. It was found that seven antigenic binding sites are simultaneously reactive on the surface of the enzyme in the presence of a large excess of antibodies or of their Fab fragments. After cyanogen bromide cleavage, the antigenic reactivity is distributed on several fragments of various sizes. 相似文献
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E. Tal E. Superstine G. G. Sulman 《Cellular and molecular life sciences : CMLS》1971,27(11):1299-1300
Zusammenfassung Dehydrotachysterol (DHT 500 µg/kg/24 h) erhöht den TSH- und T-4-Spiegel in Rattenserum bei normalen und hohen Temperaturen, ohne den Calcium-Spiegel zu verändern, und verhindert den Tod von Ratten, die bei 34° oder 37°C gehalten werden. Das Überleben der Ratten nach DHT-Injektionen erklärt sich durch erhöhte T-4-Produktion, die einen negativen «Feedback» auf den Hypothalamus ausübt und so die lethale Überproduktion von TSH verhindert.
This study was generously aided by a grant from the Dr.Gerald Kaplan family, Kfar Shmaryahu (Israel). 相似文献
This study was generously aided by a grant from the Dr.Gerald Kaplan family, Kfar Shmaryahu (Israel). 相似文献
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Summary In vertebrae of genetically selected sucrose-fed diabetic rats a statistically significant bone deficit was found after diabetes had been present for about 8 months. No osteopenia was observed in diabetic rats following treatment with estrogenic hormone for 5–7 months. The development of osseous centers in the end plates of the vertebrae was retarded in diabetic rats, but was about normal in diabetic rats given estrogen.—No differences were noted in the growth zones or in the tendency to develop articular lesions in rats of the various groups. Possible differences in the amount of GAG in intervertebral discs of diabetic and non-diabetic rats respectively await further confirmation.These investigations were aided by grant No. 2 RO1 EYO 1837-03, of the Institute of Arthritis and Metabolic Disease, National Institutes of Health, Bethesda, Maryland, USA.We are indebted to Professor Dr J. Rüttner, Institute of Pathology, University of Zürich, for his permission to use the calculator. 相似文献
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J. M. Yon 《Cellular and molecular life sciences : CMLS》1997,53(7):557-567
In this review, the main concepts of protein folding, as deduced from both theoretical and experimental in vitro studies,
are presented. The thermodynamic aspects from Anfinsen's postulate, Levinthal's paradox to the concept of folding funnel as
proposed by Wolynes and coworkers are described. Concerning the folding pathway(s), particular attention is brought to bear
on the early steps that initiate the process in the light of the results of the fast and even ultrafast techniques presently
being used. The role of structural domains as folding units is discussed. Last, from the recent studies, it can be concluded
that the main rules deduced from the in vitro folding studies are valid for the folding of a nascent polypeptide chain in
vivo. 相似文献
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Via A Ferrè F Brannetti B Helmer-Citterich M 《Cellular and molecular life sciences : CMLS》2000,57(13-14):1970-1977
Many methods have been developed to analyse protein sequences and structures, although less work has been undertaken describing and comparing protein surfaces. Evolution can lead sequences to diverge or structures to change topology; nevertheless, surface determinants that are essential to protein function itself may be mantained. Moreover, different molecules could converge to similar functions by gaining specific surface determinants. In such cases, sequence or structure comparisons are likely to be inadequate in describing or identifying protein functions and evolutionary relationships among proteins. Surface analysis can identify function determinants that are independent of sequence or secondary structure and can therefore be a powerful tool to highlight cases of possible convergent or divergent evolution. This kind of approach can be useful for a better understanding of protein molecular and biochemical mechanisms of catalysis or interaction with a ligand, which are usually surface dependent. Protein surface comparison, when compared to sequence or structure comparison methods, is a hard computational challenge and evaluated methods allowing the comparison of protein surfaces are difficult to find. In this review, we will survey the current knowledge about protein surface similarity and the techniques to detect it. 相似文献
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Soller M 《Cellular and molecular life sciences : CMLS》2006,63(7-8):796-819
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Résumé La méthode d'induction de fibrillation auriculaire par l'acétylcholine est couramment utilisée pour tester l'action de substances anti-arythmiques. Nous avons modifié cette méthode de telle sorte que la fibrillation peut être induite à plusieurs reprises, à 15 minutes d'intervalle, chez le chien anesthésié. Ceci permet la détermination de l'efficacité et de la durée d'action dans des conditions bien contrôlées. 相似文献