• Journal of Life Science
• /
• v.20 no.11
• /
• pp.1603-1610
• /
• 2010

Fucoidans are sulfated fucosylated polymers from the cell wall of brown algae. We assessed the effects of Fucus evanescens fucoidan on ultraviolet-B (UVB)-induced expression of matrix metalloproteinase-1 (MMP-1) protein, mRNA, and promoter, and the phosphorylation of mitogen-activated protein kinases in vitro using an immortalized human keratinocyte cell line. Pretreatment with 10 and $100\;{\mu}g/ml$ fucoidan significantly inhibited UVB-induced MMP-1 protein, mRNA and promoter activity, compared to UVB irradiation alone. Extracellular signal regulated kinase activation was markedly inhibited by treatment with fucoidan, though c-JUN N-terminal kinase activity and p38 activation were only marginally affected by fucoidan. F. evanescens fucoidan may be a potential therapeutic agent for the prevention and treatment of skin photoaging.

• Korean Journal of Agricultural Science
• /
• v.38 no.4
• /
• pp.673-680
• /
• 2011

The aim of this study was to identify the polymorphism on fatty acid binding protein (FABP4) gene promoter region and its association with carcass traits in Hanwoo. We performed PCR-direct sequencing of FABP4 promoter region to identify single nucleotide polymorphism (SNPs) using unrelated 24 Hanwoo bulls. Four SNPs (-298A>G, -472A>G, -887A>G, -862A>G) were detected in the promoter region and genotyped on 583 Hanwoo steers. A linear mixed model revealed an association of three SNPs (-298A>G, -472A>G and -862A>G) with carcass weight and marbling score in dominance model (P<0.05). The animals with AA genotypes for the three SNPs were heavier carcass weight (5 kg) than animals with GG genotypes in the statistical analysis. For the marbling score, the AA genotype was lower effect of marbling score (0.21) than GG genotypes. In conclusion, this study indicates an important role for three SNPs detected in promoter region of FABP4 in determining carcass weight and marbling score in Hanwoo.

• Journal of Life Science
• /
• v.18 no.4
• /
• pp.461-466
• /
• 2008

Transforming growth $factor-{\beta}$ ($TGF-{\beta}$)-dependent apoptosis is important in the elimination of damaged or abnormal cells from normal tissues in vivo. Gadd45b has been known to participate in $TGF-{\beta}-induced$ apoptosis by the activation of p38 kinase. In this report, we show that Gadd45b is an immediate-early response gene for $TGF-{\beta}$ during apoptosis in EpH4 cells. To elucidate the molecular mechanism of $TGF-{\beta}-induced$ Gadd45b gene expression, we cloned the 5'-flanking region of the mouse Gadd45b gene. When transfected into EpH4 cells, this 5'-flanking region conferred promoter activity and inducibility by $TGF-{\beta}$. Deletion analyses demonstrated that the minimal promoter activity was detected in the proximal region 220 bp upstream of the transcription initiation site. We also found that the proximal Gadd45b promoter is activated by $TGF-{\beta}$ through the action of Smad2, Smad3, and Smad4. Finally, we show that the expression of Gadd45b gene by $TGF-{\beta}$ is suppressed in EpRas cells in which $TGF-{\beta}$ could not induce apoptosis, suggesting that Gadd45b may be a crucial target for $TGF-{\beta}-induced$ apoptosis in EpH4 cells.

• Journal of Life Science
• /
• v.16 no.6
• /
• pp.1066-1070
• /
• 2006

Smooth muscle cell (SMC) proliferation is important in the pathogenesis of vascular proliferative disorders. Understanding of the molecular mechanism underlying SMC growth after arterial injury would have therapeutic implications. Here we report that receptor activator of $NF-{\kappa}B$ ligand (RANKL), a member of tumor necrosis factor (TNF) family, promotes the proliferation of SMC, leading to decreased expression of p21 and enhancement of SMC growth. ERK and p38 phosphorylation was enhanced after RANKL treatment in SMC. Inhibition of ERK/p38 MAPK activity by PD98059/SB203580 completely abolished RANKL-induced proliferation of SMC, indicating ERK and p38 MAPK are essential for RANKL-induced SMC proliferation. Taken together, our findings demonstrate that RANK-RANKL-ERK/p38 pathway is important for proliferation of SMC and that these molecules may be the new therapeutic targets for the prevention of vascular diseases.

• Proceedings of the Zoological Society Korea Conference
• /
• 2003.08a
• /
• pp.169.4-169
• /
• 2003

No Abstract, See Full Text

• BMB Reports
• /
• v.57 no.5
• /
• pp.238-243
• /
• 2024

Bone marrow-derived mesenchymal stem cells (BM-MSCs) can differentiate into endothelial cells in an inflammatory microenvironment. However, the regulatory mechanisms underlying this process are not entirely understood. Here, we found that TIE2 in BM-MSCs was upregulated at the transcriptional level after stimulation with tumor necrosis factor-alpha (TNFα), a major pro-inflammatory cytokine. Additionally, the STAT-binding sequence within the proximal region of TIE2 was necessary for TNFα-induced TIE2 promoter activation. TIE2 and STAT3 knockdown reduced TNFα-induced endothelial tube formation in BM-MSCs. Among the major TNFα-activated MAP kinases (ERK1/2, JNK1/2, and p38 MAPK) in BM-MSCs, only inhibition of the p38 kinase abrogated TNFα-induced TIE2 upregulation by inhibiting the JAK-STAT signaling pathway. These findings suggest that p38 MAP contributes to the endothelial differentiation of BM-MSCs by activating the JAK-STAT-TIE2 signaling axis in the inflammatory microenvironment.

• BMB Reports
• /
• v.38 no.4
• /
• pp.457-467
• /
• 2005

Open reading frame (ORF) 3 on the Choristoneura fumiferana granulovirus (ChfuGV), located in the 11 kb fragment of the BamHI genomic bank encodes a predicted 32-kDa putative kinase protein. Bioinformatics analysis on the predicted amino acid sequence of ChfuGV PK-1 revealed the existence of 11 catalytic subdomains. Sequence analysis within the 5'-untranslated region (5'-UTR) of ChfuGV pk-1 indicates the presence of both putative early and late promoter motifs, indicating that pk-1 may be expressed throughout the infection cycle. Promoter sequence analysis reveals that pk-1 is deprived of a TATA box and appears instead to be regulated by other cis-acting transcriptional regulatory elements. Temporal transcription analysis by RT-PCR confirms the appearance of transcripts detected from 2 h p.i. until 72 h p.i. Northern blot hybridization characterizes pk-1 transcription as a 1.2 kb transcript. Homology comparisons reveal that ChfuGV PK-1 protein is most closely related to Phthorimaea operculalla granulovirus (PoGV) with 80% amino acid identity.

• Molecules and Cells
• /
• v.43 no.1
• /
• pp.34-47
• /
• 2020

The circadian clock regulates various physiological processes, including bone metabolism. The nuclear receptors Reverbs, comprising Rev-erbα and Rev-erbβ, play a key role as transcriptional regulators of the circadian clock. In this study, we demonstrate that Rev-erbs negatively regulate differentiation of osteoclasts and osteoblasts. The knockdown of Rev-erbα in osteoclast precursor cells enhanced receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation, as well as expression of nuclear factor of activated T cells 1 (NFATc1), osteoclast-associated receptor (OSCAR), and tartrate-resistant acid phosphatase (TRAP). The overexpression of Rev-erbα leads to attenuation of the NFATc1 expression via inhibition of recruitment of c-Fos to the NFATc1 promoter. The overexpression of Rev-erbα in osteoblast precursors attenuated the expression of osteoblast marker genes including Runx2, alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OC). Rev-erbα interfered with the recruitment of Runx2 to the promoter region of the target genes. Conversely, knockdown of Rev-erbα in the osteoblast precursors enhanced the osteoblast differentiation and function. In addition, Rev-erbα negatively regulated osteoclast and osteoblast differentiation by suppressing the p38 MAPK pathway. Furthermore, intraperitoneal administration of GSK4112, a Rev-erb agonist, protects RANKL-induced bone loss via inhibition of osteoclast differentiation in vivo. Taken together, our results demonstrate a molecular mechanism of Rev-erbs in the bone remodeling, and provide a molecular basis for a potential therapeutic target for treatment of bone disease characterized by excessive bone resorption.

• Proceedings of the Korean Society of Toxicology Conference
• /
• 2003.05a
• /
• pp.95.1-95
• /
• 2003

Ginger (Zingiber officinale Roscoe, Zingiberaceae) has a wide array of pharmacologic effects. Our previous studies have demonstrated that [6]-gingerol, a major pungent ingredient of ginger, inhibits mouse skin tumor promotion and anchorage-independent growth of cultured mouse epidermal cells stimulated with epidermal growth factor. In this study, we have investigated the molecular mechanisms underlying chemopreventive effects of [6]-gingerol on mouse skin carcinogenesis. Cyclooxygenase-2 (COX-2), a key enzyme in the formation of prostaglandins, has been recognized as a molecular target of many chemopreventive as well as anti-inflammatory agents. The murine COX-2 promoter contains several transcriptional elements, particularly those involved in regulating inflammatory processes. One of the essential transcription factors responsible for COX-2 induction is NF-kappa B. Topical application of [6]-gingerol inhibited the COX-2 expression through suppression of NF-kappa B activation in phorbol ester-treated mouse skin. [6]-Gingerol, through down-regulation of p38 MAPK, abrogated the DNA binding activity of NF-kappa B by blocking phosphorylation of p65/RelA at the Ser 536 residue. These findings suggest that [6]-gingerol exerts an anti-tumor promotional activity through inhibition of the p38 MAPK-NF-kappa B siganling cascade in mouse skin.

• BMB Reports
• /
• v.38 no.3
• /
• pp.281-289
• /
• 2005

Tumor necrosis factor (TNF) signaling is mediated via two distinct receptors, TNFR2 and TNFR1, which shows partially overlapping signaling mechanisms and biological roles. In the present study, TNFR2 and TNFR1 signal transduction mechanisms involved in activation of $NF{\kappa}B$ and CMV promoter-enhancer were compared with respect to their susceptibility towards inhibitors of intracellular signaling. For this, we used SW480 cells, where we have shown that TNF-signaling can occur independently through each of the two receptors. The TNFR1 response was inhibited by D609, bromophenacyl bromide (BPB), nordihydroguararetic acid (NDGA), and by sodium salicylate, while TNFR2-mediated activation of $NF{\kappa}B$ and CMV promoter-enhancer was resistant to these compounds. The signaling mechanisms known to be affected by these inhibitors include phospholipases as well as redox- and pH-sensitive intracellular components. Our results imply that TNFR2 signaling involved in $NF{\kappa}B$ activation proceeds independently of these inhibitor-sensitive signaling components, indicating distinct signaling pathways not shared with TNFR1.