• International Journal of Oral Biology
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• v.44 no.4
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• pp.144-151
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• 2019

Alopecia has emerged as one of the biggest interests in modern society. Many studies have focused on the treatment of alopecia, such as transplantation of hair follicles or inhibition of the androgen pathway. Hair growth is achieved through proper proliferation of the components such as keratinocytes and dermal papilla cells (DPCs), movement, and interaction between the two cells. The present study examined the effect of the hedgehog (Hh) signaling pathway, which is an important and fundamental signal in the cell, on the morphology and the viability of human keratinocytes and DPCs. Upregulation of Hh signaling caused a morphological change and an increase in epithelium-mesenchymal transition-related gene expression but reduced the viability of keratinocytes, while the alteration of Hh signaling did not cause any change in DPCs. The results show the possibility that the regulation of Hh signaling can be applied for the treatment of alopecia.

• The Korea Journal of Herbology
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• v.22 no.1
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• pp.89-94
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• 2007

Objectives : The purpose of this study is to investigate cisplatin-induced apoptosis by ethanol extract of bojungbangam-tang (EBJT). Methods : To evaluate of anti-apoptic effects of EBJT, we examined several kinds of cell populations such as $CD4^{+}$ T cells, $CD8^{+}$ T cells and macrophages in spleen. Result : 1. EBJT inhibited cisplatin-induced cell death in spleen. 2. EBJT inhibited the death of $CD4^{+}$ and $CD8^{+}$ T cells. 3. EBJT slightly recovered the number of macrophages by cisplatin. Furthermore, cisplatin-induced upregulation of class II were inhibited by EBJT. Conclusion : EBJT prevented cisplatin-induced cell death, which could provide a clinical basic for side effects of anti-tumor therapeutics.

• BMB Reports
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• v.42 no.1
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• pp.28-34
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• 2009

To understand the molecular mechanism underlying proline accumulation in Brassica napus, cDNAs encoding ${\Delta}^1$-pyrroline-5-carboxylate synthetase (BnP5CS), ornithine $\delta$-aminotransferase (BnOAT) and proline dehydrogenase (BnPDH) were isolated and characterized. Southern blot analysis of BnP5CSs in B. napus and its diploid ancestors suggested a gene loss may have occurred during evolution. The expression of BnP5CS1 and BnP5CS2 was induced, while the expression of BnPDH was inhibited under salt stress, ABA treatment and dehydration, prior to proline accumulation. The upregulation of BnOAT expression was only detected during prolonged severe osmotic stress. Our results indicate that stress-induced proline accumulation in B. napus results from the reciprocal action of activated biosynthesis and inhibited proline degradation. Whether the ornithine pathway is activated depends on the severity of stress. During development, proline content was high in reproductive organs and was accompanied by markedly high expression of BnP5CS and BnPDH, suggesting possible roles of proline during flower development.

• BMB Reports
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• v.49 no.7
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• pp.370-375
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• 2016

Ras oncoproteins are small molecular weight GTPases known for their involvement in oncogenesis, which operate in a complex signaling network with multiple effectors. Approximately 25% of human tumors possess mutations in a member of this family. The Raf1/MEK/Erk1/2 pathway is one of the most intensively studied signaling mechanisms. Different levels of regulation account for the inactivation of MAP kinases by MAPK phosphatases in a cell type- and stimuli-dependent manner. In the present study, using three inducible Ras-expressing NIH/3T3 cell lines, we demonstrated that MKP3 upregulation requires the activation of the Erk1/2 pathway, which correlates with the shutdown of this pathway. We also demonstrated, by applying pharmacological inhibitors and effector mutants of Ras, that induction of MKP3 at the protein level is positively regulated by the oncogenic Ras/Raf/MEK/Erk1/2 signaling pathway.

• BMB Reports
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• v.50 no.9
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• pp.466-471
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• 2017

The results of this study show that c-Jun N-terminal kinase (JNK) activation was associated with the enhancement of docetaxel-induced cytotoxicity by simvastatin in DU145 human prostate cancer cells. To better understand the basic molecular mechanisms, we investigated simvastatin-regulated targets during simvastatin-induced cell death in DU145 cells using two-dimensional (2D) proteomic analysis. Thus, vimentin, Ras-related protein Rab-1B (RAB1B), cytoplasmic hydroxymethylglutaryl-CoA synthase (cHMGCS), thioredoxin domain-containing protein 5 (TXNDC5), heterogeneous nuclear ribonucleoprotein K (hnRNP K), N-myc downstream-regulated gene 1 (NDRG1), and isopentenyl-diphosphate Delta-isomerase 1 (IDI1) protein spots were identified as simvastatin-regulated targets involved in DU145 cell death signaling pathways. Moreover, the JNK inhibitor SP600125 significantly inhibited the upregulation of NDRG1 and IDI protein levels by combination treatment of docetaxel and simvastatin. These results suggest that NDRG1 and IDI could at least play an important role in DU145 cell death signaling as simvastatinregulated targets associated with JNK activation.

• Biomolecules & Therapeutics
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• v.9 no.3
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• pp.156-161
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• 2001

Inflammation is a frequent radiation-induced following therapeutic irradiation. Treatment of human umbilical endothelial cells (HUVEC) with ${\gamma}$-irradiation (${\gamma}$IR) induces the expression of adhesion proteins such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Since the upregulation of these proteins on endothelial cell surface has been known to be associated with inflammation, interfering with the expression of adhesion molecules is an important therapeutic target. In the present study, we demonstrate that bioflavonoid rutin inhibits ${\gamma}$IR induced expression of ICAM-1, VCAM-1, and E-selectin on HUVEC in a dose- and time dependent manner. Rutin also inhibited ${\gamma}$IR induced production of NO. These data suggest that rutin has therapeutic potential for the treatment of various inflammatory disorder associated with an increase of endothelial leukocyte adhesion molecules.

• Biomolecules & Therapeutics
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• v.24 no.5
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• pp.482-488
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• 2016

Cancer stem cells (CSCs) are a subset of tumor cells, which are characterized by resistance against chemotherapy and environmental stress, and are known to cause tumor relapse after therapy. A number of molecular mechanisms underlie the chemoresistance of CSCs, including high expression levels of drug efflux transporters. We investigated the role of the antioxidant transcription factor NF-E2-related factor 2 (NRF2) in chemoresistance development, using a CSC-enriched colonosphere system. HCT116 colonospheres were more resistant to doxorubicin-induced cell death and expressed higher levels of drug efflux transporters such as P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) compared to HCT116 monolayers. Notably, levels of NRF2 and expression of its target genes were substantially elevated in colonospheres, and these increases were linked to doxorubicin resistance. When NRF2 expression was silenced in colonospheres, Pgp and BCRP expression was downregulated, and doxorubicin resistance was diminished. Collectively, these results indicate that NRF2 activation contributes to chemoresistance acquisition in CSC-enriched colonospheres through the upregulation of drug efflux transporters.

• Molecules and Cells
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• v.37 no.12
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• pp.881-887
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• 2014

Cell proliferation is tightly controlled by the cell-cycle regulatory proteins, primarily by cyclins and cyclin-dependent kinases (CDKs) in the $G_1$ phase. The ankyrin repeat-rich membrane spanning (ARMS) scaffold protein, also known as kinase D-interacting substrate of 220 kDa (Kidins 220), has been previously identified as a prominent downstream target of neurotrophin and ephrin receptors. Many studies have reported that ARMS/Kidins220 acts as a major signaling platform in organizing the signaling complex to regulate various cellular responses in the nervous and vascular systems. However, the role of ARMS/Kidins220 in cell proliferation and cell-cycle progression has never been investigated. Here we report that knockdown of ARMS/Kidins220 inhibits mouse neuroblastoma cell proliferation by inducing slowdown of cell cycle in the $G_1$ phase. This effect is mediated by the upregulation of a CDK inhibitor p21, which causes the decrease in cyclin D1 and CDK4 protein levels and subsequent reduction of pRb hyperphosphorylation. Our results suggest a new role of ARMS/Kidins220 as a signaling platform to regulate tumor cell proliferation in response to the extracellular stimuli.

• Korean Journal of Ecology and Environment
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• v.40 no.4
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• pp.489-494
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• 2007

Transcriptional modulation of metallothionein (MT) during acute metal exposures (cadmium, copper or zinc) was examined in fry of Hemibarbus mylodon, a threatened fish species in Korean peninsula. Viability of H. mylodon fry was most affected by copper exposure (up to 79% of mortality at 1 ppm for 48 hours) and considerably by cadmium exposure (21 to 54% of mortality). On the other hand, Zn showed the least adverse effect on the viability (0 to 13% of mortality) of this species. Based on the semi-quantitative RT-PCR analysis, the stimulation of MT mRNA in response to metal exposures followed generally in a dose-dependent fashion where cadmium was the most potent inducer for the induction of MT transcripts in fry (up to more than 5-fold) while the lowest response was observed in zinc-exposed group (2-fold at maximum). From the exposure using environmentally realistic doses of cadmium (0 to 0.05 ppm for 24 hours), MT expression at mRNA level was also sensitively modulated toward upregulation up to more than 3-fold as relative to non-exposed control. Results from the present study would be a good basis for understanding the adaptive capacity and stress physiology of this endangered fish species during metal pollution.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7393-7400
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• 2015

Matrix metalloproteinase (MMP) 9, a key member of multifunctional family of zinc dependent endopeptidases has been found to be upregulated during inflammation and in some cancers. MMPs cleave extracellular matrix (ECM) proteins and play critical roles in cellular apoptosis, angiogenesis, tumor growth and metastasis. Several genetic polymorphisms have been identified that show allele specific effects on MMP9 regulation and are associated with gastric cancer, the fourth most common malignancy in the world. Besides Helicobacter pylori infection, genetic predisposition is another documented risk factor for gastric carcinoma. The single nucleotide polymorphism (SNP) at position -1562C/T of MMP9 results in the modulation for binding of transcription factors to the MMP9 gene promoter and thereby causes differences in protein expression and enzymatic activity. MMP9 transcriptional regulation during gastric cancer development remains poorly known although several studies have demonstrated associations between MMP9 -1562 C/T polymorphism with different diseases. Knowledge on mechanisms of MMP9 upregulation during gastric cancer may provide new paradigm in diagnostics and therapeutics.