611 research outputs found
Curcumin induces expression of 15-hydroxyprostaglandin dehydrogenase in gastric mucosal cells and mouse stomach in vivo: AP-1 as a potential target
15-Hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the conversion of oncogenic prostaglandin E-2 to non-tumerigenic 15-keto prostaglandin E-2. In the present study, we found that curcumin, a yellow coloring agent present in the rhizome of Curcuma Tonga Linn (Zingiberaceae), induced expression of 15-PGDH at the both transcriptional and translational levels in normal rat gastric mucosal cells. By using deletion constructs of 15-PGDH promoter, we were able to demonstrate that activator protein-1 (AP-1) is the principal transcription factor responsible for regulating curcumin-induced 15-PGDH expression. Curcumin enhanced the expression of c-jun and cFos that are functional subunits of AP-1, in the nuclear fraction of cells. Silencing of c-jun suppressed curcumin-induced expression of 15-PGDH. Moreover, the chromatin immunoprecipitation assay revealed curcumin-induced binding of c-Jun to the AP-1 consensus sequence present in the 15-PGDH promoter. Curaimin increased phosphorylation of ERK1/2 and JNK. and pharmacologic inhibition of these kinases abrogated the curcumin-induced phosphorylation of clun and 15-PGDH expression. In contrast, tetrahydrocurcumin which lacks the alpha,beta-unsaturated carbonyl group failed to induce 15-PGDH expression, suggesting that the electrophilic carbonyl group of curcumin is essential for its induction of 15-PGDH expression. Curcumin restored the expression of 15-PGDH which is down-regulated by Helicobater pylori through suppression of DNA methyltransferase 1. In addition, oral administration of curcumin increased the expression of 15-PGDH and its regulators such as p-ERK1/2, p-JNK and c-Jun in the mouse stomach. Taken together, these findings suggest that curcumin-induced upregulation of 15-PGDH may contribute to chemopreventive effects of this phytochemical on inflammation-associated gastric carcinogenesis. (C) 2020 Elsevier Inc. All rights reserved.
A Photometric and Spectroscopic Study of the Short-Period Algol EW Bo\"{o}tis with a Sct Pulsator
In this paper, we present TESS photometry and high-resolution spectra of the
short-period Algol EW Boo. We obtained double-lined radial velocities (RVs)
from the time-series spectra and measured the effective temperature of the
primary star as = 8560 118 K. For the orbital period
study, we collected all times of minima available for over the last 30 years.
It was found that the eclipse timing variation of the system could be
represented by a periodic oscillation of 17.6 0.3 years with a
semi-amplitude of 0.0041 0.0001 d. The orbital and physical parameters
were derived by simultaneously analyzing the TESS light and RV curves using the
Wilson-Devinney (WD) binary star modeling code. The component masses and radii
were showed over 3% precision: = 2.67 0.08 M,
= 0.43 0.01 M, = 2.01 0.02 R, and
= 1.35 0.01 R. Furthermore, multiple frequency
analyses were performed for the light-curve residuals from the WD model. As a
result, we detected 17 pressure-mode pulsations in the region of 40.15 - 52.37
d. The absolute dimensions and pulsation characteristics showed that the
Sct pulsator was the more massive and hotter primary star of the EW
Boo.Comment: 27 pages, 8 figures, Accepted for publication in A
High Extracellular Calcium Increased Expression of Ank, PC-1 andOsteopontin in Mouse Calvarial Cells
In the process of bone remodeling, mineral phase of bone
is dissolved by osteoclasts, resulting in elevation of calcium
concentration in micro-environment. This study was performed
to explore the effect of high extracellular calcium
(Ca
2+
e) on mineralized nodule formation and on the expression
of progressive ankylosis (Ank), plasma cell membrane
glycoprotein-1 (PC-1) and osteopontin by primary cultured
mouse calvarial cells. Osteoblastic differentiation and mineralized
nodule formation was induced by culture of mouse
calvarial cells in osteoblast differentiation medium containing
ascorbic acid and β-glycerophosphate. Although Ank, PC-1
and osteopontin are well known inhibitors of mineralization,
expression of these genes were induced at the later stage of
osteoblast differentiation during when expression of osteocalcin,
a late marker gene of osteoblast differentiation, was
induced and mineralization was actively progressing. High
Ca
2+
e (10 mM) treatment highly enhanced mRNA expression
of Ank, PC-1 and osteopontin in the late stage of osteoblast
differentiation but not in the early stage. Inhibition of p44/42
MAPK activation but not that of protein kinase C suppressed
high Ca
2+
e-induced expression of Ank, PC-1 and
osteopontin. When high Ca
2+
e (5 mM or 10 mM) was present
in culture medium during when mineral deposition was
actively progressing, matrix calcifiation was significantly
increased by high Ca
2+
e. This stimulatory effect was abolished
by pyrophosphate (5 mM) or levamisole (0.1-0.5 mM), an
alkaline phosphatase inhibitor. In addition, probenecid (2mM),
an inhibitor of Ank, suppressed matrix calcification in both
control and high Ca
2+
e-treated group, suggesting the possible
role of Ank in matrix calcification by osteoblasts. Taken
together, these results showed that high Ca
2+
e stimulates expression of Ank, PC-1 and osteopontin as well as matrix
calcification in late differentiation stage of osteoblasts and
that p44/42 MAPK activation is involved in high Ca
2+
e-
induced expression of Ank, PC-1 and osteopontin
PDbase: a database of Parkinson's Disease-related genes and genetic variation using substantia nigra ESTs
Background: Parkinson's disease (PD) is one of the most common neurodegenerative disorders, clinically characterized by impaired motor function. Since the etiology of PD is diverse and complex, many researchers have created PD-related research resources. However, resources for brain and PD studies are still lacking. Therefore, we have constructed a database of PD-related gene and genetic variations using the substantia nigra (SN) in PD and normal tissues. In addition, we integrated PD-related information from several resources. Results: We collected the 6,130 SN expressed sequenced tags (ESTs) from brain SN normal tissues and PD patients SN tissues using full-cDNA library and normalized cDNA library construction methods from our previous study. The SN ESTs were clustered in 2,951 unigene clusters and assigned in 2,678 genes. We then found up-regulated 57 genes and down-regulated 48 genes by comparing normal and PD SN ESTs frequencies with over 0.9 cut-off probability of differential expression based on the Audic and Claverie method. In addition, we integrated disease-related information from public resources. To examine the characteristics of these PD-related genes, we analyzed alternative splicing events, single nucleotide polymorphism (SNP) markers located in the gene regions, repeat elements, gene regulation elements, and pathways and protein-protein interaction networks. Conclusion: We constructed the PDbase database to capture the PD-related gene, genetic variation, and functional elements. This database contains 2,698 PD-related genes through ESTs discovered from human normal and PD patients SN tissues, and through integrating several public resources. PDbase provides the mitochondrion proteins, microRNA gene regulation elements, single nucleotide polymorphisms (SNPs) markers within PD-related gene structures, repeat elements, and pathways and networks with protein-protein interaction information. The PDbase information can aid in understanding the causation of PD. It is available at http://bioportal.kobic.re.kr/PDbase/. Supplementary data is available at http://bioportal.kobic.re.kr/PDbase/suppl.jsp. © 2009 Yang et al; licensee BioMed Central Ltdclose
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Cell Labeling and Tracking Method without Distorted Signals by Phagocytosis of Macrophages
Cell labeling and tracking are important processes in understanding biologic mechanisms and the therapeutic effect of inoculated cells in vivo. Numerous attempts have been made to label and track inoculated cells in vivo; however, these methods have limitations as a result of their biological effects, including secondary phagocytosis of macrophages and genetic modification. Here, we investigated a new cell labeling and tracking strategy based on metabolic glycoengineering and bioorthogonal click chemistry. We first treated cells with tetra-acetylated N-azidoacetyl-D-mannosamine to generate unnatural sialic acids with azide groups on the surface of the target cells. The azide-labeled cells were then transplanted to mouse liver, and dibenzyl cyclooctyne-conjugated Cy5 (DBCO-Cy5) was intravenously injected into mice to chemically bind with the azide groups on the surface of the target cells in vivo for target cell visualization. Unnatural sialic acids with azide groups could be artificially induced on the surface of target cells by glycoengineering. We then tracked the azide groups on the surface of the cells by DBCO-Cy5 in vivo using bioorthogonal click chemistry. Importantly, labeling efficacy was enhanced and false signals by phagocytosis of macrophages were reduced. This strategy will be highly useful for cell labeling and tracking
Tricho-dento-osseous Syndrome Mutant Dlx3 Shows Lower Transactivation Potential but Has Longer Half-life than Wild-type Dlx3
Dlx3 is a homeodomain protein and is known to play a role
in development and differentiation of many tissues. Deletion
of four base pairs in DLX3 (NT3198) is causally related to
tricho-dento-osseous (TDO) syndrome (OMIM #190320), a
genetic disorder manifested by taurodontism, hair abnormalities,
and increased bone density in the cranium. The
molecular mechanisms that explain the phenotypic characteristics
of TDO syndrome have not been clearly determined.
In this study, we examined phenotypic characteristics of
wild type DLX3 (wtDlx3) and 4-BP DEL DLX3 (TDO mtDlx3)
in C2C12 cells. To investigate how wtDlx3 and TDO mtDlx3
differentially regulate osteoblastic differentiation, reporter
assays were performed by using luciferase reporters containing
the promoters of alkaline phosphatase, bone sialoprotein or
osteocalcin. Both wtDlx3 and TDO mtDlx3 enhanced
significantly all the reporter activities but the effect of
mtDlx3 was much weaker than that of wtDlx3. In spite of
these differences in reporter activity, electrophoretic mobility
shift assay showed that both wtDlx3 and TDO mtDlx3
formed similar amounts of DNA binding complexes with
Dlx3 binding consensus sequence or with ALP promoter
oligonucleotide bearing the Dlx3 binding core sequence.
TDO mtDlx3 exhibits a longer half-life than wtDlx3 and it
corresponds to PESTfind analysis result showing that
potential PEST sequence was missed in carboxy terminal of
TDO mtDlx3. In addition, co-immunoprecipitation demonstrated
that TDO mtDlx3 binds to Msx2 more strongly than
wtDlx3. Taken together, though TDO mtDlx3 acted as a
weaker transcriptional activator than wtDlx3 in osteoblastic cells, there is possibility that during in vivo osteoblast
differentiation TDO mtDlx3 may antagonize transcriptional
repressor activity of Msx2 more effectively and for longer
period than wtDlx3, resulting in enhancement of osteoblast
differentiation
The Expression of Matrix Metalloprotease 20 is Stimulated by Wild Type but not by 4 bp- or 2 bp- Deletion Mutant DLX3
Mutations in DLX3 are associated with both autosomal
dominant hypoplastic hypomaturation amelogenesis
imperfecta (ADHHAI) and tricho-dento-osseous (TDO)
syndrome. ADHHAI is caused by a c.561_562delCT (2bpdel
DLX3) mutation whereas TDO syndrome is associated
with a c.571_574delGGGG (4bp-del DLX3) mutation.
However, although the causal relationships between DLX3
and an enamel phenotype have been established, the
pathophysiological role of DLX3 mutations in enamel
development has not yet been clarified. In our current study,
we prepared expression vectors for wild type and deletion
mutant DLX3 products (4bp-del DLX3, 2bp-del DLX3) and
examined the effects of their overexpression on the
expression of the enamel matrix proteins and proteases.
Wild type DLX3 enhanced the expression of matrix
metalloprotease 20 (MMP20) mRNA and protein in murine
ameloblast-like cells. However, neither a 4bp-del nor 2bpdel
DLX3 increased MMP20 expression. Wild type DLX3,
but not the above DLX3 mutants, also increased the activity
of reporters containing 1.5 kb or 0.5 kb of the MMP20
promoter. An examination of protein stability showed that
the half-life of wild type DLX3 protein was less than 12 h
whilst that of both deletion mutants was longer than 24 h.
Endogenous Dlx3 was also found to be continuously
expressed during ameloblast differentiation. Since
inactivating mutations in the gene encoding MMP20 are
associated with amelogenesis imperfecta, the inability of
4bp-del or 2bp-del DLX3 to induce MMP20 expression
suggests a possible involvement of such mutations in the enamel phenotype associated with TDO syndrome or
ADHHAI
Growth differentiation factor 11 locally controls anterior-posterior patterning of the axial skeleton.
Growth and differentiation factor 11 (GDF11) is a transforming growth factor β family member that has been identified as the central player of anterior-posterior (A-P) axial skeletal patterning. Mice homozygous for Gdf11 deletion exhibit severe anterior homeotic transformations of the vertebrae and craniofacial defects. During early embryogenesis, Gdf11 is expressed predominantly in the primitive streak and tail bud regions, where new mesodermal cells arise. On the basis of this expression pattern of Gdf11 and the phenotype of Gdf11 mutant mice, it has been suggested that GDF11 acts to specify positional identity along the A-P axis either by local changes in levels of signaling as development proceeds or by acting as a morphogen. To further investigate the mechanism of action of GDF11 in the vertebral specification, we used a Cdx2-Cre transgene to generate mosaic mice in which Gdf11 expression is removed in posterior regions including the tail bud, but not in anterior regions. The skeletal analysis revealed that these mosaic mice display patterning defects limited to posterior regions where Gdf11 expression is deficient, whereas displaying normal skeletal phenotype in anterior regions where Gdf11 is normally expressed. Specifically, the mosaic mice exhibited seven true ribs, a pattern observed in wild-type (wt) mice (vs. 10 true ribs in Gdf11-/- mice), in the anterior axis and nine lumbar vertebrae, a pattern observed in Gdf11 null mice (vs. six lumbar vertebrae in wt mice), in the posterior axis. Our findings suggest that GDF11, rather than globally acting as a morphogen secreted from the tail bud, locally regulates axial vertebral patterning
Identification of genes modulated by high extracellular calcium in coculuture of mouse osteoblasts and bone marrow cells by oligo chip assay
Calcium concentration in the bone resorption lacunae is
high and is in the mM concentration range. Both osteoblast
and osteoclast have calcium sensing receptor in the cell
surface, suggesting the regulatory role of high extracellular
calcium in bone metabolism. In vitro, high extracellular
calcium stimulated osteoclastogenesis in coculture of mouse
osteoblasts and bone marrow cells. Therefore we examined
the genes that were commonly regulated by both high
extracellular calcium and 1,25(OH)2vitaminD3 (VD3) by
using mouse oligo 11 K gene chip. In the presence of 10 mM
[Ca2+]e or 10 nM VD3, mouse calvarial osteoblasts and bone
marrow cells were co-cultured for 4 days when tartrate
resistant acid phosphatase-positive multinucleated cells
start to appear. Of 11,000 genes examined, the genes
commonly regulated both by high extracellular calcium and
by VD3 were as follows; 1) the expression of genes which
were osteoclast differentiation markers or were associated
with osteoclastogenesis were up-regulated both by high
extracellular calcium and by VD3; trap, mmp9, car2, ctsk,
ckb, atp6b2, tm7sf4, rab7, 2) several chemokine and
chemokine receptor genes such as sdf1, scya2, scyb5, scya6,
scya8, scya9, and ccr1 were up-regulated both by high
extracellular calcium and by VD3, 3) the genes such as
mmp1b, mmp3 and c3 which possibly stimulate bone
resorption by osteoclast, were commonly up-regulated, 4)
the gene such as c1q and msr2 which were related with
macrophage function, were commonly down-regulated, 5)
the genes which possibly stimulate osteoblast differentiation and/or mineralization of extracellular matrix, were
commonly down-regulated; slc8a1, admr, plod2, lox, fosb, 6)
the genes which possibly suppress osteoblast differentiation
and/or mineralization of extracellular matrix, were commonly
up-regulated; s100a4, npr3, mme, 7) the genes such
as calponin 1 and tgfbi which possibly suppress osteoblast
differentiation and/or mineralization of extracellular matrix,
were up-regulated by high extracellular calcium but were
down-regulated by VD3. These results suggest that in
coculture condition, both high extracellular calcium and
VD3 commonly induce osteoclastogenesis but suppress
osteoblast differentiation/mineralization by regulating the
expression of related genes.본 연구는 보건복지부 보건의료기술진흥사업의 지원에
의하여 이루어진 것임(03-PJ1-PG3-20500-0013)
- …