Vitamin K epoxide reductase complex subunit 1 (VKORC1): the key protein of the vitamin K cycle.

Abstract:

:Vitamin K epoxide, a by-product of the carboxylation of blood coagulation factors, is reduced to vitamin K by an enzymatic system possessing vitamin K epoxide reductase (VKOR) activity. This system is the target of coumarin-derived drugs widely used in thrombosis therapy and prophylaxis. Recently, the key protein of the VKOR system has been identified. The human VKORC1 gene maps to chromosome 16 and consists of 3 exons encoding a 163-amino acid integral ER membrane protein with three or four predicted transmembrane alpha- helices. Expression of human VKORC1 in Spodoptera frugiperda (Sf9) cells and in Pichia pastoris results in enhanced VKOR activity over low endogenous constitutive levels. Sequence based search methods reveal that human VKORC1 belongs to a large family of homologous genes found in vertebrates, insects, plants, protists, archea, and bacteria. All orthologs share five completely conserved amino acids, including two cysteines found in a tetrapeptide motif presumably required for redox function. The recent discovery of the VKORC1 gene has initiated renewed interest in understanding VKOR activity. Analysis of VKORC1 protein structure and function will be crucial in understanding the VKOR catalytic mechanism, how anticoagulant drugs modulate VKOR activity, and the role of VKORC1 in downstream physiological and pathological pathways.

journal_name

Antioxid Redox Signal

authors

Oldenburg J,Bevans CG,Müller CR,Watzka M

doi

10.1089/ars.2006.8.347

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

347-53

issue

3-4

eissn

1523-0864

issn

1557-7716

journal_volume

8

pub_type

杂志文章,评审
  • The Redox-Metabolic Couple of T Lymphocytes: Potential Consequences for Hypertension.

    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

    authors: Moshfegh CM,Case AJ

    更新日期:2020-04-30 00:00:00

  • Inhibition of Mitochondrial Fission and NOX2 Expression Prevent NLRP3 Inflammasome Activation in the Endothelium: The Role of Corosolic Acid Action in the Amelioration of Endothelial Dysfunction.

    abstract:AIMS:Corosolic acid (CRA) is a natural triterpenoid with antioxidative activity. This study was designed to elucidate the mechanism through which CRA protected vessel endothelial homeostasis by combating oxidative stress. RESULTS:In endothelial cells, CRA induced dynamin-related protein 1 (Drp1) phosphorylation at Ser...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2015.6479

    authors: Li Y,Zhou ZH,Chen MH,Yang J,Leng J,Cao GS,Xin GZ,Liu LF,Kou JP,Liu BL,Li P,Wen XD

    更新日期:2016-06-01 00:00:00

  • Human Embryonic Stem Cell-Derived Cardiovascular Progenitors Repair Infarcted Hearts Through Modulation of Macrophages via Activation of Signal Transducer and Activator of Transcription 6.

    abstract:: Aims: Human embryonic stem cell derived-cardiovascular progenitor cells (hESC-CVPCs) are a promising cell source for cardiac repair, while the underlying mechanisms need to be elucidated. We recently observed cardioprotective effects of human pluripotent stem cell (hPSC)-C...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2018.7688

    authors: Wang J,Liu M,Wu Q,Li Q,Gao L,Jiang Y,Deng B,Huang W,Bi W,Chen Z,Chin YE,Paul C,Wang Y,Yang HT

    更新日期:2019-08-10 00:00:00

  • Mitochondrial Dysfunction at the Center of Cancer Therapy.

    abstract:: Significance: Mitochondria undergo constant morphological changes through fusion, fission, and mitophagy. As the key organelle in cells, mitochondria are responsible for numerous essential cellular functions such as metabolism, regulation of calcium (Ca2+), generation of r...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2019.7898

    authors: Chiu HY,Tay EXY,Ong DST,Taneja R

    更新日期:2020-02-10 00:00:00

  • Oxidative Stress Dysregulates Protein Homeostasis Within the Male Germ Line.

    abstract:: Aims: Oxidative stress is causally linked to male reproductive pathologies, driven primarily by lipid peroxidation and an attendant production of highly reactive lipid aldehydes, such as 4-hydroxynonenal (4HNE) within the male germ line. In somatic cells, 4HNE dysregulates...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2019.7832

    authors: Cafe SL,Nixon B,Dun MD,Roman SD,Bernstein IR,Bromfield EG

    更新日期:2020-03-10 00:00:00

  • NADPH oxidase drives cytokine and neurotoxin release from microglia and macrophages in response to HIV-Tat.

    abstract::Previous reports have shown that the human immunodeficiency virus (HIV) regulatory protein Tat has both pro-oxidant and pro-inflammatory properties, suggesting that Tat might contribute to the neurological complications of HIV. However, the intracellular mechanisms whereby Tat triggers free radical production and infl...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2008.2097

    authors: Turchan-Cholewo J,Dimayuga VM,Gupta S,Gorospe RM,Keller JN,Bruce-Keller AJ

    更新日期:2009-02-01 00:00:00

  • Fatty acid-induced apoptosis in neonatal cardiomyocytes: redox signaling.

    abstract::Exposure of neonatal rat cardiac myocytes to palmitate and glucose produces apoptosis as seen by cytochrome c release, caspase 3-like activation, DNA laddering, and poly(ADP-ribose) polymerase cleavage. The purpose of this study was to understand the role of reactive oxygen species in the initiation of programmed cell...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/152308601750100524

    authors: Sparagna GC,Hickson-Bick DL,Buja LM,McMillin JB

    更新日期:2001-02-01 00:00:00

  • Cell-death-associated molecular patterns as determinants of cancer immunogenicity.

    abstract:SIGNIFICANCE:Accumulating evidence indicates that the success of some anticancer treatments (select chemotherapies or radiotherapy or trastuzumab) could be related to the stimulation of an anticancer immune response through the induction of an immunogenic tumor cell death (ICD). RECENT ADVANCES:Preclinical data reveal...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2012.5133

    authors: Ladoire S,Hannani D,Vetizou M,Locher C,Aymeric L,Apetoh L,Kepp O,Kroemer G,Ghiringhelli F,Zitvogel L

    更新日期:2014-03-01 00:00:00

  • Redox sensing by proteins: oxidative modifications on cysteines and the consequent events.

    abstract:SIGNIFICANCE:Reactive oxygen species (ROS) are not only essential for the cell's normal functions, but also mediate many pathological effects. When cells experience oxidative stress, proteins are modulated by redox changes and ultimately generate novel signaling patterns. It remains elusive how proteins are modulated, ...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2011.4313

    authors: Wang Y,Yang J,Yi J

    更新日期:2012-04-01 00:00:00

  • Synaptic mitochondrial pathology in Alzheimer's disease.

    abstract:SIGNIFICANCE:Synaptic degeneration, an early pathological feature in Alzheimer's disease (AD), is closely correlated to impaired cognitive function and memory loss. Recent studies suggest that involvement of amyloid-beta peptide (Aβ) in synaptic mitochondrial alteration underlies these synaptic lesions. Thus, to unders...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2011.4277

    authors: Du H,Guo L,Yan SS

    更新日期:2012-06-15 00:00:00

  • Synaptic Activity Protects Neurons Against Calcium-Mediated Oxidation and Contraction of Mitochondria During Excitotoxicity.

    abstract:AIMS:Excitotoxicity triggered by extrasynaptic N-methyl-d-aspartate-type glutamate receptors has been implicated in many neurodegenerative conditions, including Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke. Mitochondrial calcium overload leading to mitochondrial dysfunction repre...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2017.7092

    authors: Depp C,Bas-Orth C,Schroeder L,Hellwig A,Bading H

    更新日期:2018-10-20 00:00:00

  • Mechanosensitive production of reactive oxygen species in endothelial and smooth muscle cells: role in microvascular remodeling?

    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

    authors: Ungvari Z,Wolin MS,Csiszar A

    更新日期:2006-07-01 00:00:00

  • Disulfide bond formation in the bacterial periplasm: major achievements and challenges ahead.

    abstract:SIGNIFICANCE:The discovery of the oxidoreductase disulfide bond protein A (DsbA) in 1991 opened the way to the unraveling of the pathways of disulfide bond formation in the periplasm of Escherichia coli and other Gram-negative bacteria. Correct oxidative protein folding in the E. coli envelope depends on both the DsbA/...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2012.4864

    authors: Denoncin K,Collet JF

    更新日期:2013-07-01 00:00:00

  • Does the Cerebrospinal Fluid Reflect Altered Redox State But Not Neurotrophic Support Loss in Parkinson's Disease?

    abstract::Alteration in neurotrophic factors support and antioxidant defenses in the central nervous system (CNS) along with deficit of ferritin have been associated with idiopathic Parkinson's disease (PD). The objectives were to analyze in the cerebrospinal fluid (CSF) of patients with PD and controls the following: (i) the l...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2015.6423

    authors: Martín de Pablos A,García-Moreno JM,Fernández E

    更新日期:2015-10-10 00:00:00

  • Lipid peroxidation product 4-hydroxy-2-nonenal promotes seeding-capable oligomer formation and cell-to-cell transfer of α-synuclein.

    abstract:AIMS:Abnormal accumulation of α-synuclein aggregates is one of the key pathological features of many neurodegenerative movement disorders and dementias. These pathological aggregates propagate into larger brain regions as the disease progresses, with the associated clinical symptoms becoming increasingly severe and com...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2011.4429

    authors: Bae EJ,Ho DH,Park E,Jung JW,Cho K,Hong JH,Lee HJ,Kim KP,Lee SJ

    更新日期:2013-03-01 00:00:00

  • Ascorbic acid and sodium-dependent vitamin C transporters in the peripheral nervous system: from basic science to clinical trials.

    abstract:SIGNIFICANCE:Ascorbic acid and sodium-dependent vitamin C transporters (SVCT) have been shown to have important functions in the peripheral nervous system (PNS). Ascorbic acid is known to promote myelination in vitro in Schwann cell/dorsal root ganglion co-cultures by the formation of a collagen- and laminin-containing...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2013.5380

    authors: Gess B,Röhr D,Young P

    更新日期:2013-12-10 00:00:00

  • Isletopathy in Type 2 diabetes mellitus: implications of islet RAS, islet fibrosis, islet amyloid, remodeling, and oxidative stress.

    abstract::This review focuses primarily on islet structural and functional changes related to an activated islet renin- angiotensin system (RAS), islet oxidative-redox imbalance, the concurrence of islet fibrosis (pericapillary, intra- and peri-islet), and islet amyloid deposition (pericapillary, intra- and peri-islet). The isl...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2007.1610

    authors: Hayden MR,Sowers JR

    更新日期:2007-07-01 00:00:00

  • Peroxiredoxin 5 Decreases Beta-Amyloid-Mediated Cyclin-Dependent Kinase 5 Activation Through Regulation of Ca2+-Mediated Calpain Activation.

    abstract:AIMS:Aberrant Cdk5 (cyclin-dependent kinase 5) and oxidative stress are crucial components of diverse neurodegenerative disorders, including Alzheimer's disease (AD). We previously reported that a change in peroxiredoxin (Prx) expression is associated with protection from neuronal death. The aim of the current study wa...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2016.6810

    authors: Park J,Kim B,Chae U,Lee DG,Kam MK,Lee SR,Lee S,Lee HS,Park JW,Lee DS

    更新日期:2017-10-10 00:00:00

  • Subendocardial increase in reactive oxygen species production affects regional contractile function in ischemic heart failure.

    abstract:AIMS:Heart failure (HF) is characterized by regionalized contractile alterations resulting in loss of the transmural contractile gradient across the left ventricular free wall. We tested whether a regional alteration in mitochondrial oxidative metabolism during HF could affect myofilament function through protein kinas...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2012.4534

    authors: Andre L,Fauconnier J,Reboul C,Feillet-Coudray C,Meschin P,Farah C,Fouret G,Richard S,Lacampagne A,Cazorla O

    更新日期:2013-03-20 00:00:00

  • Oxidative modulation of K+ channels in the central nervous system in neurodegenerative diseases and aging.

    abstract:SIGNIFICANCE:Oxidative stress and damage are well-established components of neurodegenerative diseases, contributing to neuronal death during disease progression. Here, we consider key K(+) channels as target proteins that can undergo oxidative modulation, describe what is understood about how this influences disease p...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2014.6007

    authors: Peers C,Boyle JP

    更新日期:2015-02-20 00:00:00

  • The free radical theory of aging.

    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

    authors: Harman D

    更新日期:2003-10-01 00:00:00

  • Secreted Protein Acidic and Cysteine Rich Matricellular Protein Is Enriched in the Bioactive Fraction of the Human Vascular Pericyte Secretome.

    abstract:: Aims: To ascertain if human pericytes produce SPARC (acronym for Secreted Protein Acidic and Cysteine Rich), a matricellular protein implicated in the regulation of cell proliferation, migration, and cell-matrix interactions; clarify if SPARC expression in cardiac pericyte...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2019.7969

    authors: Avolio E,Mangialardi G,Slater SC,Alvino VV,Gu Y,Cathery W,Beltrami AP,Katare R,Heesom K,Caputo M,Madeddu P

    更新日期:2020-11-23 00:00:00

  • Application of in vivo ESR/spin-probe technique to monitor tumor in vivo in mouse footpad.

    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

    authors: Ichikawa K,Sakabe E,Kuninobu K,Yamori T,Tsuruo T,Yao T,Tsuneyoshi M,Utsumi H

    更新日期:2007-10-01 00:00:00

  • Lysosomal function and dysfunction: mechanism and disease.

    abstract:SIGNIFICANCE:Lysosomes are organelles in which cellular degradation occurs in a controlled manner, separated from other cellular components. As several pathways terminate in the lysosome, lysosomal dysfunction has a profound impact on cell homeostasis, resulting in manifold pathological situations, including infectious...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2011.4405

    authors: Boya P

    更新日期:2012-09-01 00:00:00

  • Histone h3 glutathionylation in proliferating mammalian cells destabilizes nucleosomal structure.

    abstract:AIMS:Here we report that chromatin, the complex and dynamic eukaryotic DNA packaging structure, is able to sense cellular redox changes. Histone H3, the only nucleosomal protein that possesses cysteine(s), can be modified by glutathione (GSH). RESULTS:Using Biotin labeled glutathione ethyl ester (BioGEE) treatment of ...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2012.5021

    authors: García-Giménez JL,Òlaso G,Hake SB,Bönisch C,Wiedemann SM,Markovic J,Dasí F,Gimeno A,Pérez-Quilis C,Palacios O,Capdevila M,Viña J,Pallardó FV

    更新日期:2013-10-20 00:00:00

  • Regulation and physiologic functions of GTPases in mitochondrial fusion and fission in mammals.

    abstract:SIGNIFICANCE:Mitochondria are double membrane-bound organelles with tubular network structures that are essential for oxidative ATP production and play pivotal roles in regulating calcium homeostasis and apoptosis. Furthermore, mitochondria produce large amounts of reactive oxygen species that are fatal to cellular fun...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2012.4830

    authors: Ishihara N,Otera H,Oka T,Mihara K

    更新日期:2013-08-01 00:00:00

  • Tight junctions in brain barriers during central nervous system inflammation.

    abstract::Homeostasis within the central nervous system (CNS) is a prerequisite to elicit proper neuronal function. The CNS is tightly sealed from the changeable milieu of the blood stream by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB). Whereas the BBB is established by specialized endo...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2011.3929

    authors: Coisne C,Engelhardt B

    更新日期:2011-09-01 00:00:00

  • Plant polyphenols regulate chemokine expression and tissue repair in human keratinocytes through interaction with cytoplasmic and nuclear components of epidermal growth factor receptor system.

    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

    authors: Pastore S,Lulli D,Fidanza P,Potapovich AI,Kostyuk VA,De Luca C,Mikhal'chik E,Korkina LG

    更新日期:2012-02-15 00:00:00

  • The redox regulation of PI 3-kinase-dependent signaling.

    abstract::Signal transduction via PI 3-kinases plays an important role in regulating the cellular processes of cell growth, survival, proliferation, and motility. The stimulated generation of reactive oxygen species is a necessary component of the signal transduction mechanisms by which many growth factors and cytokines activat...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2006.8.1765

    authors: Leslie NR

    更新日期:2006-09-01 00:00:00

  • The A640G and C242T p22(phox) polymorphisms in patients with coronary artery disease.

    abstract::Oxidative stress plays a significant role in the pathogenesis of coronary artery disease (CAD). A p22(phox)-based NAD(P)H oxidase acts as a potent superoxide-generating system in the vasculature. We studied the association of the A640G and the C242T polymorphisms with clinical risk factors, endothelial function, and s...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/15230860260220184

    authors: Zafari AM,Davidoff MN,Austin H,Valppu L,Cotsonis G,Lassègue B,Griendling KK

    更新日期:2002-08-01 00:00:00