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121.
ADMA induces monocyte adhesion via activation of chemokine receptors in cultured THP-1 cells 总被引:2,自引:0,他引:2
Asymmetric dimethylarginine (ADMA), an endogenous NOS inhibitor, is also an important inflammatory factor contributing to the development of atherosclerosis (AS). The present study was to test the effect of ADMA on angiotensin (Ang) II-induced monocytic adhesion. Human monocytoid cells (THP-1) or isolated peripheral blood monocyte cells (PBMCs) were incubated with Ang II (10−6 M) or exogenous ADMA (30 μM) for 4 or 24 h in the absence or presence of losartan or antioxidant PDTC. In cultured THP-1 cells, Ang II (10−6 M) for 24 h elevated the level of ADMA in the medium, upregulated the protein expression of protein arginine methyltransferase (PRMT) and decreased the activity of dimethylarginine dimethylaminohydrolase (DDAH). Both of Ang II and ADMA increased monocytic adhesion to human umbilical vein endothelial cells (HUVECs), elevated the levels of monocyte chemoattractant protein (MCP)-1, interleukin (IL)-8 and tumor necrosis factor (TNF)-α and upregulated CCR2 and CXCR2 mRNA expression, concomitantly with increase in reactive oxygen species (ROS) generation and activation of nuclear factor (NF)-κB. Pretreatment with losartan (10 μM) or PDTC (10 μM) abolished the effects mediated by Ang II or ADMA. In isolated PBMCs from healthy individuals, ADMA upregulated the expression of CXCR2 mRNA, which was attenuated by losartan (10 μM), however, ADMA had no effect on surface protein expression of CCR2. The present results suggest that ADMA may be involved in monocytic adhesion induced by Ang II via activation of chemokine receptors by ROS/NF-κB pathway. 相似文献
122.
Purandare AV Chen Z Huynh T Pang S Geng J Vaccaro W Poss MA Oconnell J Nowak K Jayaraman L 《Bioorganic & medicinal chemistry letters》2008,18(15):4438-4441
This study reports the identification and Hits to Leads optimization of inhibitors of coactivator associated arginine methyltransferase (CARM1). Compound 7b is a potent, selective inhibitor of CARM1. 相似文献
123.
Lorenz Katrin B. Diederichsen Ulf 《International journal of peptide research and therapeutics》2003,10(2):111-117
Summary A general strategy for the synthesis of Fmoc protected nucleobase modifed amino acids is presented. Fmoc protected nucleo
amino acids bearing a natural purine (guanine) as well as an artificial purine (isoadenine) in the side chain have been synthesized
and incorporated into cyclic pentapeptides. The structure of the cyclic peptides is based on the well known RGD peptides,
which act as selective integrin antagonists. The nucleo amino acids serve as conformationally constrained arginine mimetics
with a reduced basicity of the guanidino moiety. 相似文献
124.
Kylie M. Venardos Amanda J. Zatta Tanneale Marshall Rebecca Ritchie David M. Kaye 《Journal of cellular biochemistry》2009,108(1):156-168
Myocardial injury due to ischemia‐reperfusion (I‐R) damage remains a major clinical challenge. Its pathogenesis is complex including endothelial dysfunction and heightened oxidative stress although the key driving mechanism remains uncertain. In this study we tested the hypothesis that the I‐R process induces a state of insufficient L ‐arginine availability for NO biosynthesis, and that this is pivotal in the development of myocardial I‐R damage. In neonatal rat ventricular cardiomyocytes (NVCM), hypoxia‐reoxygenation significantly decreased L ‐arginine uptake and NO production (42 ± 2% and 71 ± 4%, respectively, both P < 0.01), maximal after 2 h reoxygenation. In parallel, mitochondrial membrane potential significantly decreased and ROS production increased (both P < 0.01). NVCMs infected with adenovirus expressing the L ‐arginine transporter, CAT1, and NVCMs supplemented with L ‐arginine both exhibited significant (all P < 0.05) improvements in NO generation and mitochondrial membrane potentials, with a concomitant significant fall in ROS production and lactate dehydrogenase release during hypoxia‐reoxygenation. In contrast, L ‐arginine deprived NVCM had significantly worsened responses to hypoxia‐reoxygenation. In isolated perfused mouse hearts, L ‐arginine infusion during reperfusion significantly improved left ventricular function after I‐R. These improved contractile responses were not dependent on coronary flow but were associated with a significant decrease in nitrotyrosine formation and increases in phosphorylation of both Akt and troponin I. Collectively, these data strongly implicate reduced L ‐arginine availability as a key factor in the pathogenesis of I‐R injury. Increasing L ‐arginine availability via increased CAT1 expression or by supplementation improves myocardial responses to I‐R. Restoration of L ‐arginine availability may therefore be a valuable strategy to ameliorate I‐R injury. J. Cell. Biochem. 108: 156–168, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
125.
Hepatocellular carcinoma (HCC) is one of the most frequently diagnosed cancers with a high mortality rate worldwide. The complexity of HCC initiation and progression poses a great challenge to the diagnosis and treatment. An increasing number of studies have focused on the emerging roles of protein arginine methylation in cancers, including tumor growth, invasion, metastasis, metabolism, immune responses, chemotherapy sensitivity, etc. The family of protein arginine methyltransferases (PRMTs) is the most important proteins that mediate arginine methylation. The deregulation of PRMTs’ expression and functions in cancers have been gradually unveiled, and many PRMTs inhibitors are in preclinical and clinical investigations now. This review focuses predominantly on the aberrant expression of PRMTs, underlying mechanisms, as well as their potential applications in HCC, and provide novel insights into HCC therapy. 相似文献
126.
脊髓性肌萎缩症(spinal muscular atrophy,SMA)是一类与运动神经元存活基因(survival of motor neurons gene,SMN gene)突变有关的神经系统变性疾病,而SMN基因的转录产物即为SMN蛋白(survival of motorneurons protein,SMN protein)。SMN蛋白与多种蛋白结合后发挥作用,如SMN-Sm蛋白的相互作用在富含尿嘧啶的小核核糖核蛋白体(uridine—richsmallribonucleo—proteins,UsnRNPs)转运装配中有重要意义。SMN蛋白是通过其Tudor结构域与剪接体sm蛋白的二甲基化修饰的富含精氨酸一氨基乙酸域(ar—ginineandglycine—rich,RG)结合。 相似文献
127.
C.I. Pereira M.V. San Romão J.S. Lolkema M.T. Barreto Crespo 《Journal of applied microbiology》2009,107(6):1894-1902
Aims: To demonstrate that the meat food strain Weissella halotolerans combines an ornithine decarboxylation pathway and an arginine deiminase (ADI) pathway and is able to produce putrescine, a biogenic amine. Evidence is shown that these two pathways produce a proton motive force (PMF). Methods and Results: Internal pH in W. halotolerans was measured with the sensitive probe 2′,7′–bis‐(2‐carboxyethyl)‐5(and‐6)‐carboxyfluorescein. Membrane potential was measured with the fluorescent probe 3,3′‐dipropylthiocarbocyanine iodine. Arginine and ornithine transport studies were made under several conditions, using cells loaded or not loaded with the biogenic amine putrescine. ADI pathway caused an increase in ΔpH dependent on the activity of F0F1ATPase. Ornithine decarboxylation pathway generates both a ΔpH and a ΔΨ. Both these pathways lead to the generation of a PMF. Conclusions: Weissella halotolerans W22 combines an ADI pathway and an ornithine decarboxylation pathway, conducing to the production of the biogenic amine putrescine and of a PMF. Transport studies suggest the existence of a unique antiporter arginine/putrescine in this lactic acid bacteria strain. Significance and Impact of the Study: The coexistence of two different types of amino acid catabolic pathways, leading to the formation of a PMF, is shown for a Weissella strain for the first time. Moreover, a unique antiport arginine/putrescine is hypothesized to be present in this food strain. 相似文献
128.
Ajay K. Mahalka 《生物化学与生物物理学报:生物膜》2009,1788(8):1600-10689
Temporins constitute a family of amphipathic α-helical antimicrobial peptides (AMP) and contain some of the shortest cytotoxic peptides, comprised of only 10-14 residues. General characteristics of temporins parallel those of other AMP, both in terms of structural features and biophysical properties relating to their interactions with membrane lipids, with selective lipid-binding properties believed to underlie the discrimination between target vs host cells. Lipid-binding properties also contribute to the cytotoxicity AMP, causing permeabilization of their target cell membranes. The latter functional property of AMP involves highly interdependent acidic phospholipid-induced conformational changes, aggregation, and formation of toxic oligomers in the membrane. These oligomers are subsequently converted to amyloid-type fibers, as demonstrated for e.g. temporins B and L in our laboratory, and more recently for dermaseptins by Auvynet et al. Amyloid state represents the generic minimum in the folding/aggregation free energy landscape, and for AMP its formation most likely serves to detoxify the peptides, in keeping with the current consensus on mature amyloid being inert and non-toxic. The above scenario is supported by sequence analyses of temporins as well as other amphipathic α-helical AMP belonging to diverse families. Accordingly, sequence comparison identifies ‘conformational switches’, domains with equal probabilities for adopting random coil, α-helical and β-sheet structures. These regions were further predicted also to aggregate and assemble into amyloid β-sheets. Taken together, the lipid-binding properties and structural characterization lend support to the notion that the mechanism of membrane permeabilization by temporins B and L and perhaps of most AMP could be very similar, if not identical, to that of the paradigm amyloid forming cytotoxic peptides, responsible for degenerative cell loss in e.g. prion, Alzheimer's and Parkinson's disease, and type 2 diabetes. 相似文献
129.
130.
Michael Tarry S.J. Ryan Arends Pietro Roversi Frank Sargent David S. Weiss Susan M. Lea 《Journal of molecular biology》2009,386(2):504-519
The Escherichia coli protein SufI (FtsP) has recently been proposed to be a component of the cell division apparatus. The SufI protein is also in widespread experimental use as a model substrate in studies of the Tat (twin arginine translocation) protein transport system. We have used SufI-GFP (green fluorescent protein) fusions to show that SufI localizes to the septal ring in the dividing cell. We have also determined the structure of SufI by X-ray crystallography to a resolution of 1.9 Å. SufI is structurally related to the multicopper oxidase superfamily but lacks metal cofactors. The structure of SufI suggests it serves a scaffolding rather than an enzymatic role in the septal ring and reveals regions of the protein likely to be involved in the protein-protein interactions required to assemble SufI at the septal ring. 相似文献