Inhibitory effect of vitamin K2 (menatetrenone) on bone resorption in ovariectomized rats: a histomorphometric and dual energy X-ray absorptiometric study.
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To clarify how vitamin K2 prevents bone loss in vivo, it was given to ovariectomized 20-week-old rats for 2 weeks. Bone mineral density (BMD) in the whole femur and in 7 specific portions (F1 to F7 from the proximal to the distal end) was determined by dual-energy X-ray absorptiometry, and histomorphometry was also performed in proximal tibial metaphysis. Ovariectomy (OVX) resulted in significant decreases in the BMD in the whole femur and the F1, F2, F6 and F7 portions. Histomorphometrical analysis of the tibia showed that the bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N) were decreased, while trabecular separation (Tb.Sp) and osteoclast number/bone surface (Oc.N/BS) were increased by OVX. The parameters for bone formation were not changed by OVX. These data indicate that the bone loss within 2 weeks is due to the enhancement of bone resorption. Vitamin K2 at 50 mg/kg inhibited the decrease in the BMD of the whole femur together with the F6 and F7 portions. Vitamin K2 also inhibited the decrease in Tb.N and the increases in Tb.Sp, Oc.N/BS and osteoclast surface/bone surface (Oc.S/BS) caused by OVX. These results suggest that vitamin K2 prevents bone loss through the inhibition of bone resorption and osteoclast formation in vivo. (+info)
Antinociceptive effect of vitamin K2 (menatetrenone) in diabetic mice.
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The antinociceptive effect of vitamin K2 (menatetrenone) in diabetic mice was examined using a tail-pressure test. Intraperitoneal injection of menatetrenone (10-100 mg/kg) produced a dose-dependent increase in the nociceptive threshold in diabetic mice. There was no significant difference between non-diabetic and diabetic mice in the menatetrenone-induced changes in the nociceptive threshold. The results suggest the therapeutical usefulness of menatetrenone for treating painful diabetic neuropathy and osteoporosis. (+info)
Inverse correlation between the changes of lumbar bone mineral density and serum undercarboxylated osteocalcin after vitamin K2 (menatetrenone) treatment in children treated with glucocorticoid and alfacalcidol.
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We have reported that alfacalcidol plus menatetrenone, a vitamin K2 with four isoprene units (menaquinone-4), treatment is useful for improving bone problems in children with skeletal unloading. The aim of this study was to evaluate the effect of menatetrenone on bone metabolism in long-term glucocorticoid-treated children with alfacalcidol treatment. Twenty children who had been treated with fixed dosages of prednisolone and alfacalcidol (0.03 microg/kg/day) for 24 weeks were enrolled in a prospective pilot study, and assigned to receive alfacalcidol (0.03 microg/kg/day) or alfacalcidol (0.03 microg/kg/day) plus menatetrenone (approximately 2 mg/kg/day). Bone biochemical markers and bone mineral density (BMD) were measured at baseline and after the 12-week treatment. In the group receiving alfacalcidol plus menatetrenone, serum carboxylated osteocalcin (OC) (p =0.0022) and lumbar BMD (p=0.0029) increased and serum undercarboxylated OC (p=0.0004) decreased significantly in comparison to the group receiving alfacalcidol; further, the change of lumbar BMD showed an inverse correlation to the change of serum undercarboxylated OC (r=-0.744, p=0.0134) and positive correlations to the baseline values of bone turnover markers such as serum levels of intact OC, bone-specific alkaline phosphatase and type I procollagen carboxyl extension peptide and urinary levels of deoxypyridinoline and N-telopeptide of type I collagen. No adverse effect was observed. This is a small short-term study, but its results suggest that menatetrenone effectively and safely increases lumbar BMD probably through carboxylation of OC in long-term prednisolone-treated children with alfacalcidol treatment who have a high bone turnover. Randomized double-blind controlled trials are needed to confirm our findings. (+info)
Quinones as the redox signal for the arc two-component system of bacteria.
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The Arc two-component signal transduction system mediates adaptive responses of Escherichia coli to changing respiratory conditions of growth. Under anaerobic conditions, the ArcB sensor kinase autophosphorylates and then transphosphorylates ArcA, a global transcriptional regulator that controls the expression of numerous operons involved in respiratory or fermentative metabolism. We show that oxidized forms of quinone electron carriers act as direct negative signals that inhibit autophosphorylation of ArcB during aerobiosis. Thus, the Arc signal transduction system provides a link between the electron transport chain and gene expression. (+info)
Construction of a Bacillus subtilis (natto) with high productivity of vitamin K2 (menaquinone-7) by analog resistance.
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To invent a functional natto promoting bone formation, the construction of a strain with high productivity of vitamin K2 (menaquinone-7: MK-7), which is important in the carboxylation of a kind of bone protein participating in bone formation, osteocalcin, was investigated. To screen for a strain appropriate to making natto (a Japanese traditional fermented soybean food) with high productivity of MK-7, a combination of analog resistance to the compounds on the biosynthetic pathway of menaquinones with mutation was done. Consequently, strain OUV23481, with 2-fold higher productivity (1,719 microg/100 g natto) of MK-7 than that of a commercial strain, was constructed as a mutant with analog resistance to 1-hydroxy-2-naphthoic acid (HNA), p-fluoro-D,L-phenylalanine (pFP), m-fluoro-D,L-phenylalanine (mFP), and beta-2-thienylalanine (betaTA). This strain was classified as Bacillus subtilis (natto). The natto made using this strain was evaluated to have a good quality as natto in all the viewpoints of appearance, flavor, taste, texture, and stringiness. (+info)
Clustering of isochorismate synthase genes menF and entC and channeling of isochorismate in Escherichia coli.
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There are two isochorismate synthase genes entC and menF in Escherichia coli. They encode enzymes (isochorismate synthase, EC 5.4.99.6) which reversibly synthesize isochorismic acid from chorismic acid. The genes share a 24.2% identity but are differently regulated. Activity of the MenF isochorismate synthase is significantly increased under anaerobic conditions whereas the activity of the EntC isochorismate synthase is greatly stimulated during growth in an iron deficient medium. Isochorismic acid synthesized by EntC is mainly channeled into enterobactin synthesis whereas isochorismic acid synthesized by MenF is mainly channeled into menaquinone synthesis. When menF or entC were separately placed onto overexpression plasmids and the plasmids introduced into a menF(-)/entC(-) double mutant in two separate experiments, the isochorismate formed was fed into both, the menaquinone and the enterobactin pathway. Moreover, in spite of a high isochorismate synthase activity menaquinone and enterobactin formation were not fully restored, indicating that isochorismate was lost by diffusion. Thus, under these conditions channeling was not observed. We conclude that in E. coli the chromosomal position of both menF and entC in their respective clusters is a prerequisite for channeling of isochorismate in both pathways. (+info)
Role of menaquinones in Fe(III) reduction by membrane fractions of Shewanella putrefaciens.
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Two Tn5-generated mutants of Shewanella putrefaciens with insertions in menD and menB were isolated and analyzed. Both mutants were deficient in the use of several terminal electron acceptors, including Fe(III). This deficiency was overcome by the addition of menaquinone (vitamin K(2)). Isolated membrane fractions from both mutants were unable to reduce Fe(III) in the absence of added menaquinone when formate was used as the electron donor. These results indicate that menaquinones are essential components for the reduction of Fe(III) by both whole cells and purified membrane fractions when formate or lactate is used as the electron donor. (+info)
Fumarate respiration of Wolinella succinogenes: enzymology, energetics and coupling mechanism.
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Wolinella succinogenes performs oxidative phosphorylation with fumarate instead of O2 as terminal electron acceptor and H2 or formate as electron donors. Fumarate reduction by these donors ('fumarate respiration') is catalyzed by an electron transport chain in the bacterial membrane, and is coupled to the generation of an electrochemical proton potential (Deltap) across the bacterial membrane. The experimental evidence concerning the electron transport and its coupling to Deltap generation is reviewed in this article. The electron transport chain consists of fumarate reductase, menaquinone (MK) and either hydrogenase or formate dehydrogenase. Measurements indicate that the Deltap is generated exclusively by MK reduction with H2 or formate; MKH2 oxidation by fumarate appears to be an electroneutral process. However, evidence derived from the crystal structure of fumarate reductase suggests an electrogenic mechanism for the latter process. (+info)