Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The characteristics of host-guest complexation between p-sulfonated calix[n]arene (SCnA, n = 4, 6) and Vitamin K(3) (VK(3)) were investigated by fluorescence spectrometry and absorption spectrometry using methylene blue (MB) as a probe. Interaction with MB and SCnA led to an obvious decrease in fluorescence intensity of MB, accompanying with shifts of emission peaks. Absorption peaks also showed interesting changes; however, when VK(3) was added, fluorescence intensity and absorbance recovered and a slight and slow red shift was observed. The obtained results showed that the inclusion ability of p-sulphonated calix[n]arenes towards VK(3) was the order: p-sulphonated calix[6]arene (SC6A) >p-sulphonated calix[4]arene (SC4A). Relative mechanism was proposed to explain the inclusion process.
Spectrochim Acta A Mol Biomol Spectrosc 2007 Sep
PMID:Study on the inclusion interaction of p-sulfonated calix[n]arenes with Vitamin K3 using methylene blue as a spectral probe. 1718 74

The intracellular NAD level plays a pivotal role in numerous biological processes such as rhythm, senescence, cancer and death. The study of the intracellular NAD level has been one of the "hotspots" in biomedical research. We investigated the effect of Vitamin K on intracellular NAD level in yeast by fluorescence spectrum in this paper. Plasma membrane redox system of yeast was found to be greatly promoted by the addition of Vitamin K(3) or Vitamin K(1). Ferricyanide reduction catalyzed by Vitamin K was accompanied by the decrease in intracellular NADH concentration and the increase in intracellular NAD level of yeast cells.
Spectrochim Acta A Mol Biomol Spectrosc 2007 May
PMID:Study the effect of Vitamin K on intracellular NAD level in yeast by fluorescence spectrum. 1725 41

Vitamin K has been known to regulate bone formation through osteocalcin synthesis by osteoblasts, which is important for mineralization and bone structure. The mechanism underlying the relationship of vitamin K with the changes of microanatomy is not fully understood, and our goal is to test whether bone deformities develop in association with vitamin K deficiency. Fish were fed a semi-purified diet containing either devoid (0.00 mg/kg diet) or adequate (40.0 mg/kg diet supplemented but 20.8 mg/kg analyzed) levels of vitamin K (menadione sodium bisulphite) for 20 weeks. At the end of 8 and 20 weeks, fish were subjected to gross examination and X-ray, and mineral content of the vertebrae was measured. The vertebrae were also subjected to histological, histomorphometric and enzyme histochemical examinations to determine the bone formation and resorption. Vitamin K deficiency primarily decreased bone mineralization and subsequently a decrease in bone mass thus resulted in an increased susceptibility to bone deformity. The occurrence of bone deformities coincided with an increased amount of osteoid tissue and decreased bone mineral content. Number of osteoblasts and osteoclasts were not affected by dietary vitamin K. In conclusion, vitamin K deficiency can impair bone mineralization and enhances bone deformities.
Comp Biochem Physiol B Biochem Mol Biol 2007 Oct
PMID:Vitamin K deficiency inhibits mineralization and enhances deformity in vertebrae of haddock (Melanogrammus aeglefinus L.). 1758 19

Vitamin K is a fat-soluble vitamin that serves as a coenzyme for vitamin K-dependent carboxylase. Besides its canonical action, vitamin K binds to the steroid and xenobiotic receptor (SXR)/pregnane X receptor (PXR) and modulates gene transcription. To determine if the osteoprotective action of vitamin K is the result of the PXR/SXR pathway, we screened by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis the PXR/SXR target genes in an osteoblastic cell line (MC3T3-E1) treated with a vitamin K2 (menaquinone 4 [MK4]). Osteoblastic differentiation of MC3T3-E1 cells was induced by MK4. Msx2, an osteoblastogenic transcription factor, was identified as an MK4-induced gene. Functional analysis of the Msx2 gene promoter mapped a vitamin K-responsive element (PXR-responsive element [PXRE]) that was directly bound by a PXR/retinoid X receptor alpha heterodimer. In a chromatin immunoprecipitation analysis, PXR was recruited together with a coactivator, p300, to the PXRE in the Msx2 promoter. MK4-bound PXR cooperated with estrogen-bound estrogen receptor alpha to control transcription at the Msx2 promoter. Knockdown of either PXR or Msx2 attenuated the effect of MK4 on osteoblastic differentiation. Thus, the present study suggests that Msx2 is a target gene for PXR activated by vitamin K and suggests that the osteoprotective action of MK4 in the human mediates, at least in part, a genomic pathway of vitamin K signaling.
Mol Cell Biol 2007 Nov
PMID:Vitamin K induces osteoblast differentiation through pregnane X receptor-mediated transcriptional control of the Msx2 gene. 2450 63

Vitamin K is known as a critical nutrient required for bone homeostasis and blood coagulation, and it is clinically used as a therapeutic agent for osteoporosis in Japan. Besides its enzymatic action as a cofactor of vitamin K-dependent gamma-glutamyl carboxylase (GGCX), we have previously shown that vitamin K(2) is a transcriptional regulator of bone marker genes and extracellular matrix-related genes, by activating the steroid and xenobiotic receptor (SXR). To explore a novel action of vitamin K in osteoblastic cells, we identified genes up-regulated by a vitamin K(2) isoform menaquinone-4 (MK-4) using oligonucleotide microarray analysis. Among these up-regulated genes by MK-4, growth differentiation factor 15 (GDF15) and stanniocalcin 2 (STC2) were identified as novel MK-4 target genes independent of GGCX and SXR pathways in human and mouse osteoblastic cells. The induction of GDF15 and STC2 is likely specific to MK-4, as it was not exerted by another vitamin K(2) isoform MK-7, vitamin K(1), or the MK-4 side chain structure geranylgeraniol. Investigation of the involved signaling pathways revealed that MK-4 enhanced the phosphorylation of protein kinase A (PKA), and the MK-4-dependent induction of both GDF15 and STC2 genes was reduced by the treatment with a PKA inhibitor H89 or siRNA against PKA. These results suggest that vitamin K(2) modulates its target gene expression in osteoblastic cells through the PKA-dependent mechanism, which may be distinct from the previously known vitamin K signaling pathways.
J Mol Endocrinol 2007 Oct
PMID:Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells. 1790 64

Vitamin K-dependent coagulation plasma proteins possess from 9-12 residues of gamma-carboxyglutamic acid (Gla) distributed over a ca. 45 amino acid peptide sequence, i.e., the Gla domain, which encompasses the NH2-terminal region. In addition, epidermal growth factor (EGF) homology units present in many of these same proteins contain beta-hydroxyaspartate (Hya) residues, which is a modification decoupled from gamma-carboxylation. The function of Gla residues in these proteins, viz., prothrombin, coagulation factors VII, IX, and X, along with anticoagulant protein C and protein S, is to coordinate Ca2+. This results in a large conformational alteration in the proteins or peptides, which allows adsorption to membrane phospholipids (PL), an event that is critical is to their proper functions in the blood coagulation system. Less certain is the role of Hya in EGF domains, but it has been proposed that modification at this residue may negatively regulate fucosylation of these regions. In several proteins, these modules also interact with Ca2+, but it has been shown that although the particular aspartate containing the beta-OH group is critical to that interaction, beta-hydroxylation of that Asp residue is not. Because of their widespread distribution, quantitative detection protocols for both Gla and Hya are of importance. It is the purpose of this communication to detail a reliable method for these analyses that is employed in our laboratories.
Methods Mol Biol 2008
PMID:gamma-Glutamate and beta-hydroxyaspartate in proteins. 1837 51

Calcitriol or 1,25(OH)(2)D(3) is a negative growth regulator of MCF-7 breast cancer cells. The growth arrest is due to apoptosis activation, which involves mitochondrial disruption. This effect is blunted in vitamin D resistant cells (MCF-7(DRes) cells). Menadione (MEN), a glutathione (GSH)-depleting compound, may potentiate antitumoral effects of anticancer drugs. The aim of this study was to investigate whether MEN enhances cellular responsiveness of MCF-7 cells to 1,25(OH)(2)D(3). Cells were cultured and treated with different concentrations of 1,25(OH)(2)D(3)+/-MEN or vehicle for 96 h. GSH levels and the activity of antioxidant enzymes were determined by spectrophotometry and ROS production by flow cytometry. Both drugs decreased growth and enhanced ROS in MCF-7 cells, obtaining the maximal effects when 1,25(OH)(2)D(3) was combined with MEN (P<0.01 vs. Control and vs. each compound alone). MCF-7(DRes) cells were not responsive to 1,25(OH)(2)D(3), but the cell proliferation was slightly inhibited by the combined treatment. Calcitriol and MEN separately enhanced antioxidant enzyme activities, but when they were used in combination, the effect was more pronounced (P<0.05 vs. Control and vs. each compound alone). MEN, calcitriol and the combined treatment decreased GSH levels (P<0.05 vs. Control). The data indicate that MEN potentiates the effect of 1,25(OH)(2)D(3) on growth arrest in MCF-7 cells by oxidative stress and increases the activities of antioxidant enzymes, probably as a compensatory mechanism.
J Steroid Biochem Mol Biol 2009 Feb
PMID:Antiproliferative action of menadione and 1,25(OH)2D3 on breast cancer cells. 1942 26

Acenocoumarol is mainly catabolized by CYP2C9 isoform of cytochrome P450 (CYP) liver complex and exerts its anticoagulant effect through the inhibition of Vitamin K Epoxide Reductase (VKOR). The most important genetic polymorphisms which lead to an impaired enzymatic activity and therefore predispose to acenocoumarol sensitivity, are considered to be CYP2C9*2 (Arg144Cys), CYP2C9*3 (Ile359Leu) and VKORC1-1639G>A, respectively. In this study we compared the results of the PGXThrombo StripAssay kit (ViennaLab Diagnostics,Vienna, Austria) with direct DNA sequencing and in house Restriction Fragment Length Polymorphisms (RFLP) for the detection of the aforementioned Single Nucleotide Polymorphisms (SNPs). The reverse hybridization StripAssay was found to be equally effective with RFLP and direct DNA sequencing for the detection of CYP2C9*2 and CYP2C9*3 polymorphisms, respectively. The comparison of the RFLP reference method with the reverse hybridization StripAssay for the detection of VKORC1-1639 G>A polymorphism showed that the reverse hybridization StripAsssay might misclassify some A/A homozygotes as heterozygotes. Optimization of the hybridization procedures may eliminate the extra low signal band observed in some samples at the reverse hybridization StripAssay and improve its diagnostic value.
Mol Biol Rep 2010 Apr
PMID:Evaluation of a reverse-hybridization StripAssay for the detection of genetic polymorphisms leading to acenocoumarol sensitivity. 1956 11

Vitamin K(2) (VK(2)) can exert cell growth inhibitory effects in various human cancer cells. In this study, we investigated the cell growth inhibitory effects of VK(2) in hepatocellular carcinoma Smmc-7721 cells and the mechanisms involved. We found that VK(2)-inhibited cell proliferation in Smmc-7721 cells in a dose-dependent manner, and the IC50 of VK(2) in Smmc-7721 cells was 9.73 microM at 24 h. The data from flow cytometric analyses, DNA fragmentation assays, and caspase 3 activity assays revealed that apoptosis was the determining factor in VK(2) activity. Furthermore, a significant increase in p53 phosphorylation and protein level was exhibited in apoptotic cells treated with VK(2), although there were no changes in p53 mRNA expression. Bax expression was unaffected by VK(2) in Smmc-7721 cells. In addition, our study showed that caspase 3 was activated by caspase 8, not caspase 9, in Smmc-7721 cells treated with VK(2). In summary, these data suggested that VK(2) can inhibit the growth of Smmc-7721 cells by induction of apoptosis involving caspase 8 activation and p53. This apoptotic process was not mediated by the intrinsic apoptotic pathway.
Mol Cell Biochem 2010 Sep
PMID:Induction of apoptosis in hepatocellular carcinoma Smmc-7721 cells by vitamin K(2) is associated with p53 and independent of the intrinsic apoptotic pathway. 2044 38

Currently, there are several lines of evidence supporting the interplay between coagulation and inflammation in the propagation of various disease processes, including venous thromboembolism (VTE) and inflammatory diseases. Major advances in the development of oral anticoagulants have resulted in considerable progress toward the goal of safe and effective oral anticoagulants that do not require frequent monitoring or dose adjustment and have minimal food/drug interactions. Indirect inhibitors such as low-molecular-weight heparin (LMWH) and the pentasaccharide fondaparinux represent improvements over traditional drugs such as unfractionated heparin for acute treatment of VTE, constituting a more targeted anticoagulant approach with predictable pharmacokinetic profiles and no requirement for monitoring. Vitamin K antagonist, with its inherent limitations in terms of multiple food and drug interactions and frequent need for monitoring, remains the only oral anticoagulant approved for long-term secondary thromboprophylaxis in VTE. The oral-direct thrombin inhibitor ximelagatran was withdrawn from the world market due to safety concerns. Newer anticoagulant drugs such as parenteral pentasaccharides (idraparinux, SSR126517E), novel oral-direct thrombin inhibitors (dabigatran), oral-direct factor Xa inhibitors (rivaroxaban, apixaban, YM-150, DU-176b), and tissue factor/factor VIIa complex inhibitors have been "tailor-made" to target specific procoagulant complexes and have the potential to greatly expand oral antithrombotic targets for both acute and long-term treatment of VTE, acute coronary syndromes, and for the prevention of stroke in atrial fibrillation patients.
Methods Mol Biol 2010
PMID:Novel anticoagulant therapy: principle and practice. 2061 17


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