Abstract:
:Prolylcarboxypeptidase isoform 1 (PRCP1) is capable of regulating numerous autocrines and hormones, such as angiotensin II, angiotensin III, αMSH1-13, and DesArg(9) bradykinin. It does so by cleaving a C-terminal PRO-X bond. Recent work also indicates that the human PRCP1 activates plasma prekallikrein (PK) to kallikrein on endothelial cells through an uncharacterized mechanism. This study aims to identify PRCP1 binding interaction and cleavage site on PK. Recently, a cDNA encoding a novel splice variant of the human PRCP1 was identified. This isoform differed only in the N-terminal region of the deduced amino acid sequence. Using structural and functional studies, a combination of peptide mapping and site-directed mutagenesis approaches were employed to investigate the interaction of PRCP1 with PK. Three PRCP peptides, in decreasing order of potency, from 1) the N-terminus of the secreted protein, 2) spanning the opening of the active site pocket, and 3) in the dimerization region inhibit PRCP activation of PK on endothelial cells. Investigations also tested the hypothesis that PRCP cleavage site on PK is between its C-terminal Pro 637 (P(637)) and Ala 638 (A(638)). Recombinant forms of PK with C-terminal alanine mutagenesis or a stop codon is activated equally as wild type PK by PRCP. In conclusion, PRCP1 interacts with PK at multiple sites for PK activation. PRCP1 also enhances FXIIa activation of PK, suggesting that its activation site on PK is not identical to that of FXIIa.
journal_name
Curr Mol Medjournal_title
Current molecular medicineauthors
Wang J,Matafonov A,Madkhali H,Mahdi F,Watson D,Schmaier AH,Gailani D,Shariat-Madar Zdoi
10.2174/1566524014666141015153519subject
Has Abstractpub_date
2014-01-01 00:00:00pages
1173-85issue
9eissn
1566-5240issn
1875-5666pii
CMM-EPUB-62867journal_volume
14pub_type
杂志文章abstract:BACKGROUND & OBJECTIVE:Interleukin 37 (IL-37) is an important regulator of the anti-inflammatory T-cell response. In this study, we investigated its expression and function in peripheral blood mononuclear cells (PBMCs) of patients with HLA-B27 associated acute anterior uveitis (AAU) and idiopathic AAU. METHODS:15 pati...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524018666180207152941
更新日期:2018-03-09 00:00:00
abstract::There is growing concern that gastrointestinal exposure to particles is associated with increased risk of toxicity to internal organs and carcinogenicity. The mechanism of action is related to particle-induced oxidative stress and oxidation of DNA. Observations from animal models indicate that gastrointestinal exposur...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652412800792624
更新日期:2012-07-01 00:00:00
abstract::Necrotic cell death has long been considered an accidental and uncontrolled mode of cell death. But recently it has become clear that necrosis is a molecularly regulated event that is associated with pathologies such as ischemia-reperfusion (IR) injury, neurodegeneration and pathogen infection. The serine/threonine ki...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652408784221306
更新日期:2008-05-01 00:00:00
abstract::Diabetic retinopathy (DR) is one of the leading causes of blindness in the working population worldwide. Vascular leakage, angiogenesis and neuronal degeneration are key features of DR. Current effective interventions for DR include treatment of systemic risk factors such as elevated blood glucose, blood pressure and ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524014666140128114414
更新日期:2014-03-01 00:00:00
abstract::Bone marrow-derived mesenchymal stem cells (BMSCs) can be recruited to tumor sites and integrate into the stroma of tumors. When co-cultured with BMSCs, otherwise weakly metastatic nasopharyngeal carcinoma cells (NPC) showed improved metastatic ability. BMSCs in the tumor environment displayed the characteristics of m...
journal_title:Current molecular medicine
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doi:10.2174/1566524014666140724102301
更新日期:2014-01-01 00:00:00
abstract:OBJECTIVE:The study aimed to evaluate the preventive effects of hydroxycitric acid(HCA) for stone formation in the glyoxylate-induced mouse model. MATERIALS AND METHODS:Male C57BL/6J mice were divided into a control group, glyoxylate(GOX) 100 mg/kg group, a GOX+HCA 100 mg/kg group, and a GOX+HCA 200 mg/kg group. Blood...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524020666200103141116
更新日期:2020-01-01 00:00:00
abstract::Pluripotent stem cells (PSCs) are powerful tools for studying developmental biology and neuronal diseases. Conventional differentiation protocols require several intermediate states and different culture conditions, inefficiently generating mixed subtypes of neuronal cells with immature characteristics. Direct program...
journal_title:Current molecular medicine
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doi:10.2174/1566524020666200421115251
更新日期:2020-04-21 00:00:00
abstract:BACKGROUND:Oxidative stress and chronic hyperglycemia are two major side effects of type 2 diabetes affecting all cell types including mesenchymal stem cells (MSCs). As a cell therapy choice, understanding the behavior of MSCs will provide crucial information for efficient treatment. METHODS:Placental mesenchymal stem...
journal_title:Current molecular medicine
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doi:10.2174/1566524019666190722115842
更新日期:2019-01-01 00:00:00
abstract::In sum, the FTIs are signal transduction inhibitors that display promising clinical activity against a broad spectrum of malignancies. We are just beginning to explore and elucidate the mechanisms by which transformed cells respond to FTIs and the optimal settings in which they do so. The clinical trials that are curr...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652405774641052
更新日期:2005-11-01 00:00:00
abstract::Sickle cell disease (SCD) and beta-thalassemia (also referred to as beta-thalassemia) are common hereditary hemoglobinopathies with differing pathophysiologies and clinical courses. However, patients with both diseases exhibit increased platelet and coagulation activation, as well as decreased levels of natural antico...
journal_title:Current molecular medicine
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更新日期:2008-11-01 00:00:00
abstract::WHIM syndrome is a dominantly inherited primary immunodeficiency disorder representing the first identified example of human disease caused by mutations in the gene encoding for the chemokine receptor CXCR4. Pathogenesis is mediated by CXCR4 hyperfunction, leading to increased responsiveness to its unique ligand CXCL1...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652411795677963
更新日期:2011-06-01 00:00:00
abstract:BACKGROUND:Dynamic epigenetic alterations accompanying CD4+ T helper cell differentiation have been implicated in multiple autoimmune diseases. The bromodomain and extra-terminal (BET) proteins are epigenetic regulators that recognize and bind to acetylated histones in chromatin and are targets for pharmacological inhi...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190126112238
更新日期:2018-01-01 00:00:00
abstract::Antisense technology exploits oligonucleotide analogs to bind to target RNAs via Watson-Crick by hybridization. Once bound, the antisense agent either disables or induces the degradation of the target RNA. Antisense agents may also be used to alter splicing. Developing antisense technology involves the creation of a n...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524043360375
更新日期:2004-08-01 00:00:00
abstract::Bitter gourd (Momordica charantia, BG) is both a nutritious and healthy food with a distinctive bitter flavor, and it is also widely exploited in folklore medicine. This review focuses on the efficacies and molecular mechanisms of BG-induced anti-diabetic, anti-HIV, and antitumor activities contributed by over twenty ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652411795976583
更新日期:2011-07-01 00:00:00
abstract::Laboratory and clinical studies have provided evidence of feasibility, safety and efficacy of cell transplantation to treat a wide variety of diseases characterized by tissue and cell dysfunction ranging from diabetes to spinal cord injury. However, major hurdles remain and limit pursuing large clinical trials, includ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652407782564381
更新日期:2007-11-01 00:00:00
abstract:BACKGROUND:Inclusion of anticancer drugs into biocompatible nanoparticulate carriers decreases the general toxicity and improves the efficacy of clinical treatments due to the reduction of soluble circulating free drug. METHODS:In addition, removal of emerging drug contaminants from wastewaters is a necessity that sho...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524021666210111104428
更新日期:2021-01-10 00:00:00
abstract::Enteroviruses are common human pathogens involved in a wide spectrum of clinical outcomes ranging from mild or non-symptomatic illness to severe diseases with neurological and/or cardiac manifestation. Despite being responsible for significant morbidity and mortality especially in immunocompromised patients and infant...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524011009060550
更新日期:2010-08-01 00:00:00
abstract:BACKGROUND:Overexpression of MDA-9/Syntenin occurs in multiple human cancer cell lines and is associated with higher grade of tumor classification, invasiveness and metastasis. In some cases, its role in cancer biology depends on relationships between MDA-9/Syntenin and NF-κB. OBJECTIVE:This study aims to analyze the ...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190104105043
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Osteoporosis is a systemic skeletal disease characterized by low bone mineral density. Vitamin D metabolism may play a pivotal role in its pathophysiology. OBJECTIVES:To determine the association between Vitamin D receptor gene polymorphisms and bone density, as well as its relation to biochemical markers o...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524019666190409122155
更新日期:2019-01-01 00:00:00
abstract::Skin is a complex tissue composed of two very different compartments -- the continuously renewing epidermis made up mostly by keratinocytes and the underlying matrix-rich dermis with the resting fibroblasts as its major cellular components. Both compartments are tightly interconnected and a paracrine mutual interactio...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524053586644
更新日期:2005-03-01 00:00:00
abstract:BACKGROUND:Lauric acid (LA) has antimicrobial effects and the potential to replace antibiotics in feeds to prevent postweaning diarrhea and increase overall swine productivity. The effects of lauric acid on the intestinal epithelial cells remain unclear. METHODS AND RESULTS:This study investigates the effects of LA on...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/1566524020666200128155115
更新日期:2020-01-01 00:00:00
abstract::Type 2 diabetes carries a 2-6-fold increased risk of cardiovascular disease (CVD) and death. Indeed, the risk of major cardiovascular events in Type 2 diabetic patients without history of coronary heart disease (CHD) is equivalent to that observed in non-diabetic subjects with CHD. However, atherosclerosis may also pr...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524053766095
更新日期:2005-05-01 00:00:00
abstract::Autophagy is a bulk cytosolic degradative process which in the last few years has become a key pathway for the advancement of molecular medicine. Autophagy (cellular self-eating) has several implications in human disorders involving accumulation of cytosolic protein aggregates such as Alzheimer, Parkinson, Huntington ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652408783769634
更新日期:2008-03-01 00:00:00
abstract::Abstract: The study of genetic alterations in tumors and their precursor lesions is often hampered by the presence of a heterogeneous background of non-neoplastic elements such as stromal cells, inflammatory cells, and angiogenic elements. Microdissection involves the extraction of specific populations of cells under ...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524013364121
更新日期:2001-03-01 00:00:00
abstract::Since the discovery almost fifteen years ago that E2F transcription factors are key targets of the retinoblastoma protein (RB), studies of the E2F family have uncovered critical roles in the control of transcription, cell cycle and apoptosis. E2F proteins are encoded by at least eight genes, E2F1 through E2F8. While s...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524010606070739
更新日期:2006-11-01 00:00:00
abstract::Despite advances in biomedical sciences, the prognosis of patients with brain tumors remains poor. Effective treatment is lacking for these central nervous system (CNS) cancers. Targeted immunotoxins are a new class of therapeutic approaches that have emerged for the treatment of human cancers. In this approach, tumor...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/156652409788970661
更新日期:2009-08-01 00:00:00
abstract::Cholesterol is a chameleon bio-molecule in cellular multiplex. It acts as a prelate in almost every cellular compartment with its site specific characteristics viz. regulation of structural veracity and scaffold fluidity of bio-membranes, insulation of electrical transmission in nerves, controlling of genes by making ...
journal_title:Current molecular medicine
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doi:10.2174/1566524020666200413112030
更新日期:2020-01-01 00:00:00
abstract::The testes are one of the most delicate organs in the male body and highly susceptible to the exogenous influences capable of inducing cell damage. Cancer therapies are well known to negatively affect the male reproductive tract with a severe impairment of spermatogenesis and infertility. The present work aimed to sys...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524016666160802150400
更新日期:2016-01-01 00:00:00
abstract::Mood disorders and schizophrenia share a number of common properties, including: genetic susceptibility; differences in brain structure and drug based therapy. Some genetic loci may even confer susceptibility for bipolar mood disorder and schizophrenia, and some atypical antipsychotic drugs are used as mood stabilizer...
journal_title:Current molecular medicine
pub_type: 杂志文章,评审
doi:10.2174/1566524033479672
更新日期:2003-08-01 00:00:00
abstract::The generation of functional neural progenitor cells (NPCs) independent of donor brain tissue and embryonic tissues is of great therapeutic interest with regard to regenerative medicine and the possible treatment of neurodegenerative disorders. Traditionally, NPCs are derived through the differentiation of embryonic s...
journal_title:Current molecular medicine
pub_type: 杂志文章
doi:10.2174/156652412798889018
更新日期:2012-02-01 00:00:00