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351.
Poly(ADP-ribosyl)ation is an immediate DNA damage-dependent posttranslational modification of histones and nuclear proteins that contributes to the survival of injured proliferating cells. Poly(ADP-ribose) polymerases (PARPs) now constitute a superfamily of 18 proteins, encoded by different genes and displaying a common conserved catalytic domain. PARP-1 (113kDa), the founding member, and PARP-2 (62kDa) are both involved in DNA-break sensing and signaling when single strand break repair (SSBR) or base excision repair (BER) pathways are engaged. The generation by homologous recombination of deficient mouse models have confirmed the caretaker function of PARP-1 and PARP-2 in mammalian cells under genotoxic stress. This review summarizes our present knowledge on their physiological role in the cellular response to DNA damage and on the genetic interactions between PARP-1, PARP-2, Atm that play an essential role during early embryogenesis. 相似文献
352.
To investigate the influence of rheumatoid arthritis on the stereoselective disposition of fenoprofen administered as a racemic mixture, eight patients with rheumatoid arthritis receiving calcium rac-fenoprofen (200 mg/8 h) and 7 healthy volunteers given single oral dose (600 mg) were investigated. Serial blood samples and urine were collected from zero to 24 h after fenoprofen (FEN) administration. The following differences were observed between the (+)-(S) and (-)-(R)-FEN in the patients with rheumatoid arthritis (means 95% CI, Wilcoxon test, P < 0.05): C(max) 14.1 (12.5-15.8) versus 3.6 (2.5-4.7) microg/ml; AUC(ss) (0-8) 80.5 (67.3-93.7) versus 12.1 (8.8-15.4) microg.h/ml; Cl(T)/f 1.3 (1.0-1.5) versus 9.1 (6.5-11.8) l/h; and t(1/2) 3.1 (2.3-3.9) versus 1.2 (0.8-1.6) h. The Cl(T)/f of (-)-(R)-FEN was reduced in patients with rheumatoid arthritis when compared to healthy volunteers: 9.1 (6.5-11.8) versus 17.4 (13.9-20.9) l/h; P < 0.05 Mann-Whitney test. The administration of rac-FEN as a single dose to healthy volunteers or multiple doses to patients with rheumatoid arthritis resulted in lower Cl(T)/f for the (+)-(S)-FEN. The lower Cl(T)/f of (-)-(R)-FEN observed for patients with rheumatoid arthritis is consistent with lower clearance by inversion, although other metabolic pathways, drug interactions, and bioavailability of the individual enantiomers may also contribute to the difference. 相似文献
353.
Silencing of both beta-TrCP1 and HOS (beta-TrCP2) is required to suppress human immunodeficiency virus type 1 Vpu-mediated CD4 down-modulation
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The human immunodeficiency virus type 1 (HIV-1) Vpu protein interacts with CD4 within the endoplasmic reticula of infected cells and targets CD4 for degradation through interaction with β-TrCP1. Mammals possess a homologue of β-TrCP1, HOS, which is also named β-TrCP2. We show by coimmunoprecipitation experiments that β-TrCP2 binds Vpu and is able to induce CD4 down-modulation as efficiently as β-TrCP1. In two different cell lines, HeLa CD4+ and Jurkat, Vpu-mediated CD4 down-modulation could not be reversed through the individual silencing of endogenous β-TrCP1 or β-TrCP2 but instead required the two genes to be silenced simultaneously. 相似文献
354.
355.
Sequential activation of poly(ADP-ribose) polymerase 1, calpains, and Bax is essential in apoptosis-inducing factor-mediated programmed necrosis 总被引:2,自引:0,他引:2
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Moubarak RS Yuste VJ Artus C Bouharrour A Greer PA Menissier-de Murcia J Susin SA 《Molecular and cellular biology》2007,27(13):4844-4862
Alkylating DNA damage induces a necrotic type of programmed cell death through the poly(ADP-ribose) polymerases (PARP) and apoptosis-inducing factor (AIF). Following PARP activation, AIF is released from mitochondria and translocates to the nucleus, where it causes chromatin condensation and DNA fragmentation. By employing a large panel of gene knockout cells, we identified and describe here two essential molecular links between PARP and AIF: calpains and Bax. Alkylating DNA damage initiated a p53-independent form of death involving PARP-1 but not PARP-2. Once activated, PARP-1 mediated mitochondrial AIF release and necrosis through a mechanism requiring calpains but not cathepsins or caspases. Importantly, single ablation of the proapoptotic Bcl-2 family member Bax, but not Bak, prevented both AIF release and alkylating DNA damage-induced death. Thus, Bax is indispensable for this type of necrosis. Our data also revealed that Bcl-2 regulates N-methyl-N'-nitro-N'-nitrosoguanidine-induced necrosis. Finally, we established the molecular ordering of PARP-1, calpains, Bax, and AIF activation, and we showed that AIF downregulation confers resistance to alkylating DNA damage-induced necrosis. Our data shed new light on the mechanisms regulating AIF-dependent necrosis and support the notion that, like apoptosis, necrosis could be a highly regulated cell death program. 相似文献
356.
Diego Jarquín José Crossa Xavier Lacaze Philippe Du Cheyron Joëlle Daucourt Josiane Lorgeou François Piraux Laurent Guerreiro Paulino Pérez Mario Calus Juan Burgueño Gustavo de los Campos 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2014,127(3):595-607
Key message
New methods that incorporate the main and interaction effects of high-dimensional markers and of high-dimensional environmental covariates gave increased prediction accuracy of grain yield in wheat across and within environments.Abstract
In most agricultural crops the effects of genes on traits are modulated by environmental conditions, leading to genetic by environmental interaction (G × E). Modern genotyping technologies allow characterizing genomes in great detail and modern information systems can generate large volumes of environmental data. In principle, G × E can be accounted for using interactions between markers and environmental covariates (ECs). However, when genotypic and environmental information is high dimensional, modeling all possible interactions explicitly becomes infeasible. In this article we show how to model interactions between high-dimensional sets of markers and ECs using covariance functions. The model presented here consists of (random) reaction norm where the genetic and environmental gradients are described as linear functions of markers and of ECs, respectively. We assessed the proposed method using data from Arvalis, consisting of 139 wheat lines genotyped with 2,395 SNPs and evaluated for grain yield over 8 years and various locations within northern France. A total of 68 ECs, defined based on five phases of the phenology of the crop, were used in the analysis. Interaction terms accounted for a sizable proportion (16 %) of the within-environment yield variance, and the prediction accuracy of models including interaction terms was substantially higher (17–34 %) than that of models based on main effects only. Breeding for target environmental conditions has become a central priority of most breeding programs. Methods, like the one presented here, that can capitalize upon the wealth of genomic and environmental information available, will become increasingly important. 相似文献357.
358.
Maria Jimenez Giorgio Barbatelli Roberta Allevi Saverio Cinti Josiane Seydoux Jean-Paul Giacobino Patrick Muzzin Frédéric Preitner 《European journal of biochemistry》2003,270(4):699-705
White and brown adipocytes are usually located in distinct depots; however, in response to cold, brown adipocytes appear in white fat. This response is mediated by beta-adrenoceptors but there is a controversy about the subtype(s) involved. In the present study, we exposed to cold beta 3-adrenoceptor knockout mice (beta 3KO) on a C57BL/6J genetic background and measured in white adipose tissue the density of multilocular cells and the expression of the brown adipocyte marker uncoupling protein-1 (UCP1). In brown fat of beta 3KO mice, UCP1 expression levels were normal at 24 degrees C as well as after a 10-day cold exposure. Strikingly, under both conditions, in the white fat of beta 3KO mice the levels of UCP1 mRNA and protein as well as the density of multilocular cells were decreased. These results indicate that beta 3-adrenoceptors play a major role in the appearance of brown adipocytes in white fat and suggest that the brown adipocytes present in white fat differ from those in brown fat. 相似文献
359.
Suellen Serafini Maria Mercês Santos Ana Cristina Aoun Tannuri Maria Claudia Nogueira Zerbini Maria Cecília de Mendonça Coelho Josiane de Oliveira Gonçalves Uenis Tannuri 《Diagnostic pathology》2017,12(1):84