Abstract:
:Oxygen-regulated protein 150 kD (ORP150) is a novel endoplasmic-reticulum-associated chaperone induced by hypoxia/ischemia. Although ORP150 was sparingly upregulated in neurons from human brain undergoing ischemic stress, there was robust induction in astrocytes. Cultured neurons overexpressing ORP150 were resistant to hypoxemic stress, whereas astrocytes with inhibited ORP150 expression were more vulnerable. Mice with targeted neuronal overexpression of ORP150 had smaller strokes compared with controls. Neurons with increased ORP150 demonstrated suppressed caspase-3-like activity and enhanced brain-derived neurotrophic factor (BDNF) under hypoxia signaling. These data indicate that ORP150 is an integral participant in ischemic cytoprotective pathways.
journal_name
Nat Medjournal_title
Nature medicineauthors
Tamatani M,Matsuyama T,Yamaguchi A,Mitsuda N,Tsukamoto Y,Taniguchi M,Che YH,Ozawa K,Hori O,Nishimura H,Yamashita A,Okabe M,Yanagi H,Stern DM,Ogawa S,Tohyama Mdoi
10.1038/85463keywords:
subject
Has Abstractpub_date
2001-03-01 00:00:00pages
317-23issue
3eissn
1078-8956issn
1546-170Xpii
85463journal_volume
7pub_type
杂志文章相关文献
NATURE MEDICINE文献大全abstract::We have designed short peptides composed of two functional domains, one a tumor blood vessel 'homing' motif and the other a programmed cell death-inducing sequence, and synthesized them by simple peptide chemistry. The 'homing' domain was designed to guide the peptide to targeted cells and allow its internalization. T...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/12469
更新日期:1999-09-01 00:00:00
abstract::Altered metabolism has been implicated in the pathogenesis of inflammatory diseases. NADPH oxidase 4 (NOX4), a source of cellular superoxide anions, has multiple biological functions that may be of importance in inflammation and in the pathogenesis of human metabolic diseases, including diabetes. However, the mechanis...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4153
更新日期:2016-09-01 00:00:00
abstract::Cold exposure may be a potential therapy for diabetes by increasing brown adipose tissue (BAT) mass and activity. Here we report that 10 d of cold acclimation (14-15 °C) increased peripheral insulin sensitivity by ∼43% in eight type 2 diabetes subjects. Basal skeletal muscle GLUT4 translocation markedly increased, wit...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3891
更新日期:2015-08-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature medicine
pub_type: 已发布勘误
doi:10.1038/s41591-019-0562-8
更新日期:2019-09-01 00:00:00
abstract::Genetic variants of human and simian immunodeficiency virus (HIV and SIV) that evolve during the course of infection and progression to AIDS are phenotypically and antigenically distinct from their progenitor viruses present at early stages of infection. However, it has been unclear how these late variants, which are ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/8414
更新日期:1999-05-01 00:00:00
abstract::Hutchinson-Gilford progeria syndrome (HGPS) is a childhood premature aging disease caused by a spontaneous point mutation in lamin A (encoded by LMNA), one of the major architectural elements of the mammalian cell nucleus. The HGPS mutation activates an aberrant cryptic splice site in LMNA pre-mRNA, leading to synthes...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1204
更新日期:2005-04-01 00:00:00
abstract::Neurofibrillary tangles (NFTs), composed of truncated and hyperphosphorylated tau, are a common feature of numerous aging-related neurodegenerative diseases, including Alzheimer's disease (AD). However, the molecular mechanisms mediating tau truncation and aggregation during aging remain elusive. Here we show that asp...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3700
更新日期:2014-11-01 00:00:00
abstract::To determine the protective potential of the humoral immune response against HIV-1 in vivo we evaluated the potency of three neutralizing antibodies (2G12, 2F5 and 4E10) in suppressing viral rebound in six acutely and eight chronically HIV-1-infected individuals undergoing interruption of antiretroviral treatment (ART...
journal_title:Nature medicine
pub_type: 临床试验,杂志文章
doi:10.1038/nm1244
更新日期:2005-06-01 00:00:00
abstract::Pulmonary hypertension (PH) is characterized by increased proliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs). Forkhead box O (FoxO) transcription factors are key regulators of cellular proliferation. Here we show that in pulmonary vessels and PASMCs of human and experimental PH lun...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3695
更新日期:2014-11-01 00:00:00
abstract::Efforts to identify and annotate cancer driver genetic lesions have been focused primarily on the analysis of protein-coding genes; however, most genetic abnormalities found in human cancer are located in intergenic regions. Here we identify a new long range-acting MYC enhancer controlled by NOTCH1 that is targeted by...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3665
更新日期:2014-10-01 00:00:00
abstract::Expression of the oncogenic transcription factor MYC is disproportionately elevated in triple-negative breast cancer (TNBC), as compared to estrogen receptor-, progesterone receptor- or human epidermal growth factor 2 receptor-positive (RP) breast cancer. We and others have shown that MYC alters metabolism during tumo...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4055
更新日期:2016-04-01 00:00:00
abstract::Rapid and accurate measurement of biomarkers in tissue and fluid samples is a major challenge in medicine. Here we report the development of a new, miniaturized diagnostic magnetic resonance (DMR) system for multiplexed, quantitative and rapid analysis. By using magnetic particles as a proximity sensor to amplify mole...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.1711
更新日期:2008-08-01 00:00:00
abstract::In the version of this article originally published, there was an error in the legend for Extended Data Fig. 7. The legend for panel f was originally: "f, FACS analysis of IL7R-, CD62L- and CD45RA- expression on TRAC-1928ζ and TRAC-1XX CAR T cells at day 63 post CAR infusion (representative for at least n = 3 mice per...
journal_title:Nature medicine
pub_type: 已发布勘误
doi:10.1038/s41591-019-0360-3
更新日期:2019-03-01 00:00:00
abstract::Inducible nitric oxide synthase (iNOS) is a transcriptionally regulated enzyme that synthesizes nitric oxide from L-arginine that has a key role in the pathophysiology of systemic inflammation and sepsis. Transgenic animals with a null mutation for the iNOS gene are resistant to hypotension and death caused by Escheri...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0596-581
更新日期:1996-05-01 00:00:00
abstract::The mechanisms that regulate hematopoietic stem cell (HSC) regeneration after myelosuppressive injury are not well understood. We identified epidermal growth factor (EGF) to be highly enriched in the bone marrow serum of mice bearing deletion of Bak and Bax in TIE2-expressing cells in Tie2Cre; Bak1(-/-); Bax(flox/-) m...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3070
更新日期:2013-03-01 00:00:00
abstract::Infection with Plasmodium falciparum during pregnancy leads to the accumulation of parasite-infected erythrocytes in the placenta, and is associated with excess perinatal mortality, premature delivery and intrauterine growth retardation in the infant, as well as increased maternal mortality and morbidity. P. falciparu...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/71582
更新日期:2000-01-01 00:00:00
abstract::Levels of insulin-like growth factor I (IGF-I), a neuroprotective hormone, decrease in serum during aging, whereas amyloid-beta (Abeta), which is involved in the pathogenesis of Alzheimer disease, accumulates in the brain. High brain Abeta levels are found at an early age in mutant mice with low circulating IGF-I, and...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1202-793
更新日期:2002-12-01 00:00:00
abstract::The mechanism by which angiogenic factors recruit bone marrow (BM)-derived quiescent endothelial and hematopoietic stem cells (HSCs) is not known. Here, we report that functional vascular endothelial growth factor receptor-1 (VEGFR1) is expressed on human CD34(+) and mouse Lin(-)Sca-1(+)c-Kit(+) BM-repopulating stem c...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm740
更新日期:2002-08-01 00:00:00
abstract::Huntington's disease is caused by an expanded polyglutamine repeat in the huntingtin protein (HTT), but the pathophysiological sequence of events that trigger synaptic failure and neuronal loss are not fully understood. Alterations in N-methyl-D-aspartate (NMDA)-type glutamate receptors (NMDARs) have been implicated. ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3246
更新日期:2013-08-01 00:00:00
abstract::The 55-kilodalton (kDa) protein from the E1B-region of adenovirus binds to and inactivates the p53 gene, which is mutated in half of human cancers. We have previously shown that the replication and cytopathogenicity of an E1B, 55-kDa gene-attenuated adenovirus, ONYX-015, is blocked by functional p53 in RKO and U20S ca...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0697-639
更新日期:1997-06-01 00:00:00
abstract::Proper function of the endoplasmic reticulum (ER) and mitochondria is crucial for cellular homeostasis, and dysfunction at either site has been linked to pathophysiological states, including metabolic diseases. Although the ER and mitochondria play distinct cellular roles, these organelles also form physical interacti...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3735
更新日期:2014-12-01 00:00:00
abstract::Understanding the mechanisms of osteoclastogenesis is crucial for developing new drugs to treat diseases associated with bone loss, such as osteoporosis. Here we report that the C-C chemokine receptor-2 (CCR2) is crucially involved in balancing bone mass. CCR2-knockout mice have high bone mass owing to a decrease in n...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.1945
更新日期:2009-04-01 00:00:00
abstract::Adequate lipid secretion by mammary glands during lactation is essential for the survival of mammalian offspring. However, the mechanism governing this process is poorly understood. Here we show that Cidea is expressed at high levels in lactating mammary glands and its deficiency leads to premature pup death as a resu...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2614
更新日期:2012-01-15 00:00:00
abstract::Autoimmune T-helper cells drive pathogenic autoantibody production in systemic lupus erythematosus (SLE), but the mechanisms maintaining those T cells are unknown. Autoreactive T cells are normally eliminated by functional inactivation (anergy) and activation-induced cell death (AICD) or apoptosis through death recept...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1005
更新日期:2004-04-01 00:00:00
abstract::Recent years have seen an explosion in the rate of discovery of genetic defects linked to Parkinson's disease. These breakthroughs have not provided a direct explanation for the disease process. Nevertheless, they have helped transform Parkinson's disease research by providing tangible clues to the neurobiology of the...
journal_title:Nature medicine
pub_type: 杂志文章,评审
doi:10.1038/nm1068
更新日期:2004-07-01 00:00:00
abstract::With the goal of modeling human disease of the large intestine, we sought to develop an effective protocol for deriving colonic organoids (COs) from differentiated human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs). Extensive gene and immunohistochemical profiling confirmed that the derived C...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4355
更新日期:2017-07-01 00:00:00
abstract::The role of nitric oxide (NO) in the genesis of cerebral malaria is controversial. Most investigators propose that the unfortunate consequence of the high concentrations of NO produced to kill the parasite is the development of cerebral malaria. Here we have tested this high NO bioavailability hypothesis in the settin...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1499
更新日期:2006-12-01 00:00:00
abstract::The gene encoding the lysine-specific histone methyltransferase KMT2D has emerged as one of the most frequently mutated genes in follicular lymphoma and diffuse large B cell lymphoma; however, the biological consequences of KMT2D mutations on lymphoma development are not known. Here we show that KMT2D functions as a b...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3943
更新日期:2015-10-01 00:00:00
abstract::The live tuberculosis vaccines Mycobacterium bovis BCG (bacille Calmette-Guérin) and Mycobacterium microti both lack the potent, secreted T-cell antigens ESAT-6 (6-kDa early secretory antigenic target) and CFP-10 (10-kDa culture filtrate protein). This is a result of independent deletions in the region of deletion-1 (...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm859
更新日期:2003-05-01 00:00:00
abstract::It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene1. The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches2-5. For patients in whom WES is uninformative...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-019-0457-8
更新日期:2019-06-01 00:00:00