Abstract:
:Hypoxia-inducible factor (HIF) is a transcriptional activator that promotes death or survival in neurons. The regulators and targets of HIF-1alpha-mediated death remain unclear. We found that prodeath effects of HIF-1 are not attributable to an imbalance in HIF-1alpha and HIF-1beta expression. Rather, the synergistic death caused by oxidative stress and by overexpression of an oxygen-resistant HIF-VP16 in neuroblasts was attributable to transcriptional upregulation of BH3-only prodeath proteins, PUMA or BNIP3. By contrast, overexpression of BNIP3 was not sufficient to potentiate oxidative death. As acidosis is known to activate BNIP3-mediated death, we examined other secondary stresses, such as oxidants or prolyl hydroxylase activity are necessary for exposing the prodeath functions of HIF in neurons. Antioxidants or prolyl hydroxylase inhibition prevented potentiation of death by HIF-1alpha. Together, these studies suggest that antioxidants and PHD inhibitors abrogate the ability of HIF-mediated transactivation of BH3-only proteins to potentiate oxidative death in normoxia. The findings offer strategies for minimizing the prodeath effects of HIF-1 in neurologic conditions associated with hypoxia and oxidative stress, such as stroke and spinal cord injury.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Aminova LR,Siddiq A,Ratan RRdoi
10.1089/ars.2008.2039subject
Has Abstractpub_date
2008-12-01 00:00:00pages
1989-98issue
12eissn
1523-0864issn
1557-7716journal_volume
10pub_type
杂志文章abstract:SIGNIFICANCE:Ionizing radiation is a vital component in the oncologist's arsenal for the treatment of cancer. Approximately 50% of all cancer patients will receive some form of radiation therapy as part of their treatment regimen. DNA is considered the major cellular target of ionizing radiation and can be damaged dire...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2012.5000
更新日期:2014-04-01 00:00:00
abstract:SIGNIFICANCE:Studies of sporadic cases, toxin models, and genetic causes of Parkinson's disease suggest that mitochondrial dysfunction may be an early feature of pathogenesis. RECENT ADVANCES:Compelling evidence of a causal relationship between mitochondrial function and disease was found with the identification of se...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2011.4019
更新日期:2012-05-01 00:00:00
abstract:AIMS:The usefulness of estrogen replacement therapy (ERT) in preventing oxidative stress associated with menopause is controversial. We aimed to study if there is a critical time window for effective treatment of the effects of ovariectomy with estrogens at the molecular, metabolic, and cellular level. RESULTS:Our mai...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.5112
更新日期:2014-01-10 00:00:00
abstract::Changes in the hemodynamic environment (e.g., hypertension, increased blood flow/shear stress) are known to lead to vascular remodeling; however, the underlying mechanisms by which hemodynamic forces control gene expression in vascular cells are not yet completely understood. This review considers how mechanosensitive...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2006.8.1121
更新日期:2006-07-01 00:00:00
abstract::The decision to remove or refold oxidized, denatured, or misfolded proteins by heat shock protein 70 and its binding partners is critical to determine cell fate under pathophysiological conditions. Overexpression of the ubiquitin ligase C-terminus of HSC70 interacting protein (CHIP) can compensate for failure of other...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3300
更新日期:2011-05-15 00:00:00
abstract::The nuclear factor-kappaB (NF-kappaB) is a transcription factor that plays a pivotal role in the induction of genes involved in physiological processes, as well as in the response to inflammation. In this study, we used a selective nonpeptidyl superoxide dismutase mimetic, M40403, to investigate the role of superoxide...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/1523086041361659
更新日期:2004-08-01 00:00:00
abstract:SIGNIFICANCE:Evidence is emerging that parenteral administration of high-dose vitamin C may warrant development as an adjuvant therapy for patients with sepsis. RECENT ADVANCES:Sepsis increases risk of death and disability, but its treatment consists only of supportive therapies because no specific therapy is availabl...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2013.5401
更新日期:2013-12-10 00:00:00
abstract:: Significance: Genomic instability, a hallmark of cancer, renders cancer cells susceptible to genomic stress from both endogenous and exogenous origins, resulting in the increased tendency to accrue DNA damage, chromosomal instability, or aberrant DNA localization. Apart fr...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2020.8221
更新日期:2020-12-04 00:00:00
abstract:SIGNIFICANCE:Cystic fibrosis (CF) is the most common lethal genetic disorder in the Caucasian people. It is due to the mutation of cystic fibrosis transmembrane conductance regulator (CFTR) gene located on the long arm of the chromosome 7, which encodes for CFTR protein. The latter, an adenosine triphosphate binding ca...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2014.6012
更新日期:2015-03-01 00:00:00
abstract::Redox dysregulation originating from metabolic alterations and dependence on mitogenic and survival signaling through reactive oxygen species represents a specific vulnerability of malignant cells that can be selectively targeted by redox chemotherapeutics. This review will present an update on drug discovery, target ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2009.2541
更新日期:2009-12-01 00:00:00
abstract::Gamma-interferon-inducible lysosomal thiol reductase (GILT) is constitutively expressed in most antigen presenting cells and is interferon γ inducible in other cell types via signal transducer and activator of transcription 1. Normally, N- and C-terminal propeptides are cleaved in the early endosome, and the mature pr...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3684
更新日期:2011-08-01 00:00:00
abstract::Aging is the accumulation of changes that increase the risk of death. Aging changes can be attributed to development, genetic defects, the environment, disease, and an inborn process: the aging process. The latter is the major risk factor for disease and death after age 28 in the developed countries. In these countrie...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/152308603770310202
更新日期:2003-10-01 00:00:00
abstract::This work rests on our previous report (J Cereb Blood Flow Metab 30: 1275-1287, 2010) recognizing that glutamate (Glu) oxaloacetate transaminase (GOT) is induced when brain tissue hypoxia is corrected during acute ischemic stroke (AIS). GOT can metabolize Glu into tricarboxylic acid cycle intermediates and may therefo...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2011.3930
更新日期:2011-05-15 00:00:00
abstract::The tumor suppressor p53 protects organisms from most types of cancer through multiple mechanisms. The p53 gene encodes a stress-activated transcriptional factor that transcriptionally regulates a large set of genes with versatile functions. These p53-activated genes mitigate consequences of stress regulating cell via...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2010.3530
更新日期:2011-09-15 00:00:00
abstract:SIGNIFICANCE:Extranuclear sirtuins in cytosol (SIRT2) and mitochondria (SIRT3, SIRT4, and SIRT5) are key regulators of metabolic enzymes and the antioxidative defense mechanisms. They play an important role in the adjustment of metabolic pathways in alterations of the nutritional status. Recent Advances: Recent studies...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2017.7270
更新日期:2018-03-10 00:00:00
abstract:AIM:TNF (tumor necrosis factor)-related apoptosis-inducing ligand (TRAIL), is a selective killer of tumor cells, although its potential is limited by the development of resistance. In this article, we investigated whether the polyherbal preparation Zyflamend(®) can sensitize tumor cells to TRAIL. RESULTS:We found that...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2011.3982
更新日期:2012-03-01 00:00:00
abstract::The redox status of tumors inoculated into the footpads of mice was investigated by using an in vivo ESR/spin-probe technique. A single-cell suspension of a metastatic subclone of colon carcinoma NL-17 was inoculated into the footpads of Balb/c mice. At 12, 24, 48, and 96 h after the inoculation, a spin probe, either ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2007.1719
更新日期:2007-10-01 00:00:00
abstract::NADPH oxidase is known to modulate the arterial tone, but the role of its specific subunits is still unclear. The objective of this study was to compare the role of p47 and gp91phox (NOX2) on artery dilatation. We conducted a multicenter study enrolling 30 patients with chronic granulomatous disease (CGD) (25 with NOX...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.4987
更新日期:2013-04-20 00:00:00
abstract::Fluid shear stress is intimately linked with vascular oxidative stress and atherosclerosis. We posited that atherogenic oscillatory shear stress (OSS) induced mitochondrial superoxide (mtO2•-) production via NADPH oxidase and c-Jun NH(2)-terminal kinase (JNK-1 and JNK-2) signaling. In bovine aortic endothelial cells, ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2010.3645
更新日期:2011-09-01 00:00:00
abstract:: Significance: Excessive and prolonged proinflammatory responses are associated with oxidative stress, which is commonly observed during chronic tuberculosis (TB). Such condition favors tissue destruction and consequently bacterial spread. A tissue remodeling program is als...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2020.8124
更新日期:2021-02-20 00:00:00
abstract:: Significance: T lymphocytes, as part of the adaptive immune system, possess the ability to activate and function in extreme cellular microenvironments, which requires these cells to remain highly malleable. One mechanism in which T lymphocytes achieve this adaptability is ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2020.8042
更新日期:2020-04-30 00:00:00
abstract:AIMS:Endothelium-dependent vasorelaxation is mediated by endothelium-derived relaxing factor and endothelium-derived hyperpolarizing factor (EDHF). However, the molecular entity of EDHF remains unclear. The present study examined whether hydrogen sulfide (H₂S) acts as EDHF and how H₂S mediates EDHF pathways from endoth...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2012.4805
更新日期:2013-11-10 00:00:00
abstract::This brief review first touches on the origins of the earth's oxygen. It then identifies and locates the principal oxygen sensor in vertebrates, the carotid body (CB). The CB is unique in that in human subjects, it is the only sensor of lower than normal levels in the partial pressure of oxygen (hypoxia, HH). Another ...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2007.1546
更新日期:2007-06-01 00:00:00
abstract:SIGNIFICANCE:Development of donor-specific antibodies (DSA) after kidney transplantation is associated with reduced allograft survival. A few strategies have been tested in controlled clinical trials for the treatment of antibody-mediated rejection (AMR), and no therapies are approved by regulatory authorities. Thus de...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2014.5892
更新日期:2014-12-10 00:00:00
abstract:AIMS:To evaluate mechanisms underlying modulation of inflammatory chemokines in primary human keratinocytes (normal human epidermal keratinocytes) and repair-related processes in wound models by plant polyphenols (PPs) with antioxidant and superoxide scavenging properties (verbascoside [Vb], resveratrol [Rv], polydatin...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2011.4053
更新日期:2012-02-15 00:00:00
abstract::Mitochondria contain two aqueous compartments: the matrix and the intermembrane space. Whereas many of the biologic functions of the matrix were well characterized in the past, it became clear very recently that the intermembrane space plays a pivotal role in the coordination of mitochondrial activities with other cel...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2009.3063
更新日期:2010-11-01 00:00:00
abstract:SIGNIFICANCE:Alzheimer's disease is a neurodegenerative disorder that is projected to exceed more than 100 million cases worldwide by 2050. Aging is considered the primary risk factor for some 90% of Alzheimer's cases but a significant 10% of patients suffer from aggressive, early-onset forms of the disease. There is c...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2016.6802
更新日期:2016-12-01 00:00:00
abstract::Molecular chaperones play key roles in protein quality control, signal transduction, proliferation, and cell death, and confer cytoprotection and assure survival after environmental stress. The heat-shock response is implicated in a variety of conditions including ischemic diseases, infection and immunity, neurodegene...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2007.1866
更新日期:2008-01-01 00:00:00
abstract::The protein kinase C (PKC) isozyme family plays key roles in cell growth regulation and influences neoplastic disease development and progression. For example, PKCepsilon is oncogenic, and PKCdelta tumor-suppressive. PKC isozymes are characterized by distinct activation mechanisms entailing phosphatidylserine-dependen...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章
doi:10.1089/ars.2005.7.855
更新日期:2005-07-01 00:00:00
abstract:SIGNIFICANCE:Protein degradation has been identified as being deregulated in numerous human diseases. Hence, proteins involved in proteasomal as well as lysosomal degradation are regarded as interesting potential drug targets and are thoroughly investigated in clinical studies. RECENT ADVANCES:Technical advances in th...
journal_title:Antioxidants & redox signaling
pub_type: 杂志文章,评审
doi:10.1089/ars.2011.4393
更新日期:2012-09-01 00:00:00