Abstract：
:Cellular oxygen partial pressure is sensed by a family of prolyl-4-hydroxylase domain (PHD) enzymes that modify hypoxia-inducible factor (HIF)alpha subunits. Upon hydroxylation under normoxic conditions, HIFalpha is bound by the von Hippel-Lindau tumor suppressor protein and targeted for proteasomal destruction. Since PHD activity is dependent on oxygen and ferrous iron, HIF-1 mediates not only oxygen- but also iron-regulated transcriptional gene expression. Here we show that copper (CuCl(2)) stabilizes nuclear HIF-1alpha under normoxic conditions, resulting in hypoxia-response element (HRE)-dependent reporter gene expression. In in vitro hydroxylation assays CuCl(2) inhibited prolyl-4-hydroxylation independently of the iron concentration. Ceruloplasmin, the main copper transport protein in the plasma and a known HIF-1 target in vitro, was also induced in vivo in the liver of hypoxic mice. Both hypoxia and CuCl(2) increased ceruloplasmin (as well as vascular endothelial growth factor [VEGF] and glucose transporter 1 [Glut-1]) mRNA levels in hepatoma cells, which was due to transcriptional induction of the ceruloplasmin gene (CP) promoter. In conclusion, our data suggest that PHD/HIF/HRE-dependent gene regulation can serve as a sensory system not only for oxygen and iron but also for copper metabolism, regulating the oxygen-, iron- and copper-binding transport proteins hemoglobin, transferrin, and ceruloplasmin, respectively.
journal_name
Bloodjournal_title
Bloodauthors
Martin F,Linden T,Katschinski DM,Oehme F,Flamme I,Mukhopadhyay CK,Eckhardt K,Tröger J,Barth S,Camenisch G,Wenger RHdoi
10.1182/blood-2004-10-3980subject
Has Abstractpub_date
2005-06-15 00:00:00pages
4613-9issue
12eissn
0006-4971issn
1528-0020pii
2004-10-3980journal_volume
105pub_type
杂志文章相关文献
BLOOD文献大全abstract：:An immunotoxin specific for human T lymphocytes was prepared by coupling an IgG2a anti-CD3 murine monoclonal antibody (64.1) to purified ricin A chain (64.1-A). Treatment of blood mononuclear cells with this immunotoxin at a concentration of 1.7 X 10(-9) mol/L for two hours at 37 degrees C in the presence of 20 mmol/L...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1985-10-01 00:00:00
abstract：:Sympathetic axons embedded in a few arterioles and vasa vasora were recently shown to store tissue plasminogen activator (t-PA) in vesicles. But the extension of such t-PA axons to arteries and arterioles throughout the organism has not been verified. Confirmation of this anatomy would identify a second significant so...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2005-12-4884
更新日期：2006-07-01 00:00:00
abstract：:The role of T-cell subsets in the induction of tissue factor (TF) production by human monocytes in vitro was investigated. Mitogen stimulation enabled both unfractionated T cells and their CD4+ or CD8+ subsets to promote procoagulant activity (PCA). After mitogen or antigen activation, all seven T-cell clones with Th1...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1995-07-01 00:00:00
abstract：:Several strategies can be used to manage fetal or neonatal alloimmune thrombocytopenia (FNAIT) in subsequent pregnancies. Serial fetal blood sampling (FBS) and intrauterine platelet transfusions (IUPT), as well as weekly maternal IV immunoglobulin infusion (IVIG), with or without additional corticosteroid therapy, are...
journal_title：Blood
pub_type： 杂志文章,评审
doi：10.1182/blood-2016-10-739656
更新日期：2017-03-16 00:00:00
abstract：:Both SDF-1 and CXCR4 disruption are lethal to mice at the embryonic stage and cause abnormalities in B lymphopoiesis, myelopoiesis, cardiogenesis, vasculogenesis, and cerebellar development. To investigate the role of SDF-1 and CXCR4 in hematopoiesis during the adult stage, mice reconstituted with bone marrow-derived ...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：2000-09-15 00:00:00
abstract：:Reversible interactions of glycoconjugates on leukocytes with P- and E-selectin on endothelial cells mediate tethering and rolling of leukocytes in inflamed vascular beds, the first step in their recruitment to sites of injury. Although selectin ligands on hematopoietic precursors have been identified, here we review ...
journal_title：Blood
pub_type： 杂志文章,评审
doi：10.1182/blood-2011-07-343566
更新日期：2011-12-22 00:00:00
abstract：:Currently availabel staging systems for non-Hodgkin lymphomas are not useful for clinical staging classification of most primary cutaneous lymphomas. The tumor, node, metastases (TNM) system used for mycosis fungoides (MF) and Sézary syndrome (SS) is not appropriate for other primary cutaneous lymphomas. A usable, uni...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2006-10-054601
更新日期：2007-07-15 00:00:00
abstract：:It has been proposed that CD4 T-cell responses to Staphylococcus aureus (SA) can inadvertently enhance neoplastic progression in models of skin cancer and cutaneous T-cell lymphoma (CTCL). In this prospective study, we explored the effect of transient antibiotic treatment on tumor cells and disease activity in 8 patie...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood.2018888107
更新日期：2019-09-26 00:00:00
abstract：:We sequentially studied bone marrow (BM) samples of 25 patients in complete remission of an acute lymphoblastic leukemia (ALL) using a simplified polymerase chain reaction (PCR) strategy (direct use of the PCR product as a clonogenic probe recognizing rearranged Ig heavy chain sequences) as a first approach. BM aspira...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1993-09-01 00:00:00
abstract：:We performed a pilot study to test the effectiveness of allogeneic bone marrow transplantation in the treatment of chronic myelogenous leukemia. Five patients in the advanced stages of chronic myelogenous leukemia (four in blast crisis, one in accelerated phase) with abnormal chromosomes underwent matched-sibling allo...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1981-11-01 00:00:00
abstract：:To evaluate the relationship between myeloperoxidase (MPO) gene expression and specific lineages of hematopoietic differentiation, we analyzed expression of the MPO gene in a variety of normal and leukemic human cells. As a first step, we synthesized several oligonucleotide probes and isolated cDNA clones for the MPO ...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1989-11-01 00:00:00
abstract：:The therapeutic potential of hematopoietic stem cell (HSC) gene therapy can be fully exploited only by reaching efficient gene transfer into HSCs without compromising their biologic properties. Although HSCs can be transduced by HIV-derived lentiviral vectors (LVs) in short ex vivo culture, they display low permissivi...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2005-10-4047
更新日期：2006-06-01 00:00:00
abstract：:Families with 3 different syndromes characterized by autosomal dominant inheritance of low platelet count and giant platelets were studied. Fechtner syndrome is an autosomal-dominant variant of Alport syndrome manifested by nephritis, sensorineural hearing loss, and cataract formation in addition to macrothrombocytope...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：2000-11-15 00:00:00
abstract：:To understand the regulatory mechanism of erythropoietin (EPO) receptor (EPOR) gene expression, the effect of EPO on the steady-state level of EPOR mRNA was examined using the human EPO-dependent cell line UT-7 as a model system. We found that the treatment of UT-7 cells with EPO resulted in a transient decrease of th...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1997-02-15 00:00:00
abstract：:CD8+ Foxp3+ T cells (Tregs) are a potent regulatory population whose functional and ontological similarities to CD4+ Fox3+ T cells have not been well delineated. Using an experimental model of graft-versus-host disease (GVHD), we observed that CD8+ Tregs were significantly less potent than CD4+ Tregs for the suppressi...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2017-09-807156
更新日期：2018-07-26 00:00:00
abstract：:The functions of the alphaC domains of fibrinogen in clotting and fibrinolysis, which have long been enigmatic, were determined using recombinant fibrinogen truncated at Aalpha chain residue 251. Scanning electron microscopy and confocal microscopy revealed that the fibers of alpha251 clots were thinner and denser, wi...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2005-05-2150
更新日期：2005-12-01 00:00:00
abstract：:Notch is a major factor mediating interaction between hematopoietic progenitor cells (HPCs) and bone marrow stroma (BMS). However its contribution to dendritic cell (DC) differentiation is controversial. We found that main Notch ligands Delta-1 and Jagged-1 had the opposite effect on DC differentiation. Delta-1 promot...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2006-05-025601
更新日期：2007-01-15 00:00:00
abstract：:Interferon-alpha (IFN-alpha) is considered the standard therapy for chronic myeloid leukemia (CML) patients not suitable for allogeneic stem cell transplantation. From 1987 through 1992, 195 patients in the Benelux with recent untreated CML were randomized between low-dose IFN-alpha2b (3 MIU, 5 days/wk) or hydroxyurea...
journal_title：Blood
pub_type： 临床试验,杂志文章,多中心研究,随机对照试验
doi：
更新日期：1998-04-15 00:00:00
abstract：:Leukemia inhibitory factor (LIF)/differentiation-inhibiting activity (DIA)/human interleukin for DA cells (HILDA) is a cytokine with biologic activities involving a variety of different types of target cells. Here we have tested LIF/DIA for possible effects on the growth and differentiation of normal human hematopoiet...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1990-05-15 00:00:00
abstract：:Low molecular weight heparin (LMWH) is being tested as an experimental drug for improving pregnancy outcome in women with inherited thrombophilia and placenta-mediated pregnancy complications, such as recurrent pregnancy loss. The role of thrombotic processes in these disorders remains unproven, and the issue of antit...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood-2012-08-448209
更新日期：2013-03-14 00:00:00
abstract：:We have investigated the clonality of Ph1-negative hemopoietic progenitor cells appearing in long-term marrow cultures established with cells from a mosaic Turner syndrome patient (46,XX/45,X) with Ph1-positive chronic myeloid leukemia (CML). The Ph1-positive clone had been shown previously to have arisen from a cell ...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1984-12-01 00:00:00
abstract：:Myeloma is a unique hematologic malignancy that exclusively homes in the bone marrow and induces massive osteoclastic bone destruction presumably by producing cytokines that promote the differentiation of the hematopoietic progenitors to osteoclasts (osteoclastogenesis). It is recognized that neighboring bone marrow s...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：2000-09-01 00:00:00
abstract：:There is considerable interest in identifying nontoxic differentiation inducers for the treatment of various malignant and nonmalignant blood disorders, including inborn beta-chain hemoglobinopathies. Using the human leukemic K562 cell line as a model, we explored the efficacy of phenylacetate, an amino acid derivativ...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1992-09-15 00:00:00
abstract：:The animal assay of potential new iron-chelating agents is at present dependent on cumbersome and imprecise iron balance studies in hypertransfused rodents. We report the development of a radioisotope assay in intact rats based on the transient labeling by ferritin 59Fe of the main source of chelatable iron within hep...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1981-10-01 00:00:00
abstract：:A 9-yr-old female presented with a Wilm's tumor and a coagulopathy consistent with von Willebrand's disease. Factor VIII procoagulant activity (VIII C), factor VIII related antigen (VIIIR:Ag), and von Willebrand factor activity (VIII:vWf) were decreased. There was no evidence for a circulating inhibitor of the factor ...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1981-10-01 00:00:00
abstract：:This study demonstrates that the human platelet F11 receptor (F11R) functions as an adhesion molecule, and this finding is confirmed by the structure of the protein as revealed by molecular cloning. The F11R is a 32-/35-kd protein duplex that serves as the binding site through which a stimulatory monoclonal antibody c...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：2000-04-15 00:00:00
abstract：:Human myeloma cells freshly isolated from 40 patients with IgG multiple myeloma (MM, 10 in stage I and 30 in stage III), were cultured for 48 hours with recombinant B cell stimulatory factor 2 (rBSF-2)/interleukin-6 (IL-6), which is considered a major growth factor for myeloma cells. Uptake of 3H-thymidine by these pu...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1988-08-01 00:00:00
abstract：:Obesity and inflammatory bowel disease (IBD) are systemic inflammatory disorders that predispose to arterial and venous thrombosis through similar prothrombotic mechanisms. Obesity and IBD are chronic risk factors that lead to a persistently elevated risk of thrombosis, although the thrombotic risk with IBD appears to...
journal_title：Blood
pub_type： 杂志文章,评审
doi：10.1182/blood-2016-05-716720
更新日期：2016-11-17 00:00:00
abstract：:The transcription factor nuclear factor-kappaB (NF-kappaB) confers significant survival potential in a variety of tumors. Several established or novel anti-multiple myeloma (anti-MM) agents, such as dexamethasone, thalidomide, and proteasome inhibitors (PS-341), inhibit NF-kappaB activity as part of their diverse acti...
journal_title：Blood
pub_type： 杂志文章
doi：10.1182/blood.v99.11.4079
更新日期：2002-06-01 00:00:00
abstract：:The effects of selectively depleting CD8+ cells from donor bone marrow were assessed in 36 patients receiving transplantation from an HLA-identical sibling as treatment for leukemia. Donor bone marrow underwent ex vivo treatment using anti-Leu-2 monoclonal antibody and complement. Patients received cyclosporine post-t...
journal_title：Blood
pub_type： 杂志文章
doi：
更新日期：1990-07-15 00:00:00
