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排序方式: 共有146条查询结果,搜索用时 15 毫秒
131.
Popoli P Pintor A Tebano MT Frank C Pepponi R Nazzicone V Grieco R Pèzzola A Reggio R Minghetti L De Berardinis MA Martire A Potenza RL Domenici MR Massotti M 《Journal of neurochemistry》2004,89(6):1479-1489
The aim of this work was to investigate the potential neuroprotective effects of the metabotropic glutamate receptor 5 (mGlu5R) antagonist 2-Methyl-6-(phenylethynyl)-pyridine (MPEP) towards quinolinic acid (QA)-induced striatal excitoxicity. Intrastriatal MPEP (5 nmol/0.5 micro L) significantly attenuated the body weight loss, the electroencephalographic alterations, the impairment in spatial memory and the striatal damage induced by bilateral striatal injection of QA (210 nmol/0.7 micro L). In a second set of experiments, we aimed to elucidate the mechanisms underlying the neuroprotective effects of MPEP. In microdialysis studies in naive rats MPEP (80-250 micro m through the dialysis probe) significantly reduced the increase in glutamate levels induced by 5 mm QA. In primary cultures of striatal neurons MPEP (50 micro m) reduced the toxicity induced by direct application of glutamate [measured as release of lactate dehydrogenase [LDH]). Finally, we found that 50 micro m MPEP was unable to directly block NMDA-induced effects (namely field potential reduction in corticostriatal slices, as well as LDH release and intracellular calcium increase in striatal neurons). We conclude that: (i) MPEP has neuroprotective effects towards QA-induced striatal excitotoxicity; (ii) both pre- and post-synaptic mechanisms are involved; (iii) the neuroprotective effects of MPEP do not appear to involve a direct blockade of NMDA receptors. 相似文献
132.
Sgarra L Addabbo F Potenza MA Montagnani M 《American journal of physiology. Endocrinology and metabolism》2012,302(10):E1171-E1182
Rosiglitazone is a thiazolidinedione, a synthetic PPARγ receptor agonist with insulin-sensitizing properties that is used as an antidiabetic drug. In addition to improving glycemic control through actions in metabolic target tissues, rosiglitazone has numerous biological actions that impact on cardiovascular homeostasis. Some of these actions are helpful (e.g., improving endothelial function), whereas others are potentially harmful (e.g., promoting fluid retention). Since cardiovascular morbidity and mortality are major endpoints for diabetes, it is essential to understand how the natural history of diabetes alters the net benefits and risks of rosiglitazone therapy. This complex issue is an important determinant of optimal use of rosiglitazone and is critical for understanding cardiovascular safety issues. We give special attention to the effects of rosiglitazone in diabetic patients with stable coronary artery disease and the impact of rosiglitazone actions on atherosclerosis and plaque instability. This provides a rational conceptual framework for predicting evolving benefit/risk profiles that inform optimal use of rosiglitazone in the clinical setting and help explain the results of recent large clinical intervention trials where rosiglitazone had disappointing cardiovascular outcomes. Thus, in this perspective, we describe what is known about the molecular mechanisms of action of rosiglitazone on cardiovascular targets in the context of the evolving pathophysiology of diabetes over its natural history. 相似文献
133.
Leonardo Manzoni Laura Belvisi Aldo Bianchi Annalisa Conti Carmelo Drago Marilenia de Matteo Luca Ferrante Eloise Mastrangelo Paola Perego Donatella Potenza Carlo Scolastico Federica Servida Gabriele Timpano Francesca Vasile Vincenzo Rizzo Pierfausto Seneci 《Bioorganic & medicinal chemistry》2012,20(22):6687-6708
Novel pro-apoptotic, homo- and heterodimeric Smac mimetics/IAPs inhibitors based on the N-AVPI-like 4-substituted 1-aza-2-oxobicyclo[5.3.0]decane scaffold were prepared from monomeric structures connected through a head–head (8), tail–tail (9) or head–tail (10) linker. The selection of appropriate decorating functions for the scaffolds, and of rigid and flexible linkers connecting them, is described. The synthesis, purification and analytical characterization of each prepared dimer 8–10 is thoroughly described. 相似文献
134.
Pierfausto Seneci Aldo Bianchi Cristina Battaglia Laura Belvisi Martino Bolognesi Andrea Caprini Federica Cossu Elena de Franco Marilenia de Matteo Domenico Delia Carmelo Drago Amira Khaled Daniele Lecis Leonardo Manzoni Moira Marizzoni Eloise Mastrangelo Mario Milani Ilaria Motto Elisabetta Moroni Donatella Potenza Carlo Scolastico 《Bioorganic & medicinal chemistry》2009,17(16):5834-5856
Novel proapoptotic Smac mimics/IAPs inhibitors have been designed, synthesized and characterized. Computational models and structural studies (crystallography, NMR) have elucidated the SAR of this class of inhibitors, and have permitted further optimization of their properties. In vitro characterization (XIAP BIR3 and linker-BIR2–BIR3 binding, cytotox assays, early ADMET profiling) of the compounds has been performed, identifying one lead for further in vitro and in vivo evaluation. 相似文献
135.
人HCN4通道的滞后现象:影响窦房结起搏的潜在决定因素(英文) 总被引:3,自引:0,他引:3
萧永福 Natalie Chandler Halina Dobrzynski Eric S.Richardson Erica M.TenBroek Joshua J.Wilhelm Vinod Sharma Anthony Varghese Mark R.Boyett Paul A.Iaizzo Daniel C.Sigg 《生理学报》2010,(1)
超极化活化环核苷酸门控(hyperpolarization-activated cyclic-nucleotide-gated,HCN)通道参与调制心脏跳动的节律和速率。与HCN1和HCN2有所不同,慢通道HCN4可能不存在电压依赖的滞后现象。本研究采用单细胞膜片钳方法,在稳定转染hHCN4的HEK293细胞上进行电生理记录,观察hHCN4通道是否存在滞后现象,以及cAMP对其的调制作用;同时采用实时定量RT-PCR方法检测窦房结和心房组织中HCNs的表达。电压钳实验结果显示hHCN4电流(Ih)激活随着保持电位超极化的变化而向去极化方向移动。三角电位变化钳(triangular ramp)和动作电位钳的结果也显示了hHCN4的滞后现象。cAMP增加Ih电流幅度,且使电流激活向去极化方向移动,从而改变内源性hHCN4滞后行为。RT-PCR结果显示,人窦房结组织主要表达HCN4,占75%,HCN1占21%,HCN2占3%,HCN3占0.7%。以上结果提示,人窦房结组织主要表达HCN4亚型,hHCN4的Ih存在电压依赖性的滞后现象,且受cAMP调制。由此推断,hHCN4通道的滞后现象可能在窦房结起搏活动中起到了关键作用。 相似文献
136.
Aaron MN Joiner Ben P Phillips Kumar Yugandhar Ethan J Sanford Marcus B Smolka Haiyuan Yu Elizabeth A Miller J Christopher Fromme 《The EMBO journal》2021,40(12)
The GTPase Rab1 is a master regulator of the early secretory pathway and is critical for autophagy. Rab1 activation is controlled by its guanine nucleotide exchange factor, the multisubunit TRAPPIII complex. Here, we report the 3.7 Å cryo‐EM structure of the Saccharomyces cerevisiae TRAPPIII complex bound to its substrate Rab1/Ypt1. The structure reveals the binding site for the Rab1/Ypt1 hypervariable domain, leading to a model for how the complex interacts with membranes during the activation reaction. We determined that stable membrane binding by the TRAPPIII complex is required for robust activation of Rab1/Ypt1 in vitro and in vivo, and is mediated by a conserved amphipathic α‐helix within the regulatory Trs85 subunit. Our results show that the Trs85 subunit serves as a membrane anchor, via its amphipathic helix, for the entire TRAPPIII complex. These findings provide a structural understanding of Rab activation on organelle and vesicle membranes. 相似文献
137.
138.
Dicer is a ribonuclease playing a key role in the biogenesis of microRNAs and small interfering RNAs. Here we report the identification of a novel splice variant of human dicer gene, the first one bearing a modified coding sequence. It encodes a truncated protein, t-Dicer that lacks the dsRNA-binding domain and is defective in one of the two RNase III catalytic centers. The splice variant was found in neuroblastoma cells and in cells induced to neuronal differentiation, whereas it was not detectable in other cell lines or in normal tissues. Interestingly, it occurred in primary neuroblastic tumors, mainly in stroma poor neuroblastomas. 相似文献
139.
Nicoletta Potenza 《Cell biology international》2009,33(7):734-738
Dicer and Argonaute 1-4 proteins are key components of the cytoplasmic enzyme machinery responsible for biogenesis and performance of microRNAs. To gain insight into the roles of these proteins in cell differentiation, we investigated possible changes in the expression levels of Dicer and Argonaute 1-4 genes during the differentiation of cultured neural and glial cells. The results show that the 5 genes are differentially expressed along the 2 differentiation pathways and suggest a prevalent role of Dicer and Argonaute 4 in neural cell differentiation. 相似文献
140.
Rosati Leonardo Romano Vito Antonio Cerone Luca Fascetti Simonetta Potenza Giovanna Bazzato Erika Cillo Davide Mecca Marisabel Racioppi Rocco D’Auria Maurizio Farris Emmanuele 《Journal of plant research》2019,132(1):49-56
Journal of Plant Research - The discovery of few isolated populations of Gymnospermium scipetarum (since now considered as an amphi-Adriatic endemic) in the S-Apennines prompted to investigate,... 相似文献