• 제목/요약/키워드: down-regulation

검색결과 1,254건 처리시간 0.032초

Dipeptides Inhibit Melanin Synthesis in Mel-Ab Cells through Down-Regulation of Tyrosinase

  • Lee, Hyun-E;Kim, Eun-Hyun;Choi, Hye-Ryung;Sohn, Uy-Dong;Yun, Hye-Young;Baek, Kwang-Jin;Kwon, Nyoun-Soo;Park, Kyoung-Chan;Kim, Dong-Seok
    • The Korean Journal of Physiology and Pharmacology
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    • 제16권4호
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    • pp.287-291
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    • 2012
  • This study investigated the effects of proline-serine (PS) and valine-serine (VS) dipeptides on melanogenesis in Mel-Ab cells. Proline-serine and VS significantly inhibited melanin synthesis in a concentration-dependent manner, though neither dipeptide directly inhibited tyrosinase activity in a cell-free system. Both PS and VS down-regulated the expression of microphthalmia-associated transcription factor (MITF) and tyrosinase. In a follow-up study also described here, the effects of these dipeptides on melanogenesis-related signal transduction were quantified. Specifically, PS and VS induced ERK phosphorylation, though they had no effect on phosphorylation of the cAMP response element binding protein (CREB). These data suggest that PS and VS inhibit melanogenesis through ERK phosphorylation and subsequent down-regulation of MITF and tyrosinase. Properties of these dipeptides are compatible with application as skin-whitening agents.

Down-Regulation of CYP1A1 Expression in Breast Cancer

  • Hafeez, S.;Ahmed, A.;Rashid, Asif Z.;Kayani, Mahmood Akhtar
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권5호
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    • pp.1757-1760
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    • 2012
  • Breast cancer is a major cause of death in women worldwide. Mammary tissue expressing xenobiotic metabolizing enzymes metabolically activate or detoxify potential genotoxic breast carcinogens. Deregulation of these xenobiotic metabolizing enzymes is considered to be a major contributory factor to breast cancer. The present study is focused on the expression of the xenobiotic metabolizing gene, CYP1A1, in breast cancer and its possible relationships with different risk factors. Twenty five tumors and twenty five control breast tissue samples were collected from patients undergoing planned surgery or biopsy from different hospitals. Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and western-blotting were used to investigate the expression of CYP1A1 in breast cancer control and disease samples. mRNA expression of CYP1A1 was down-regulated in 40% of breast tumor samples. Down-regulation was also observed at the protein level. Significnat relations were noted with marital status and tumour grade but not histopathological type. In conclusion, CYP1A1 protein expression was markedly reduced in tumor breast tissues samples as compared to paired control tissue samples.

Expression of Recombinant Human Growth Hormone in a Soluble Form in Escherichia coli by Slowing Down the Protein Synthesis Rate

  • Koo, Tai-Young;Park, Tai-Hyun
    • Journal of Microbiology and Biotechnology
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    • 제17권4호
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    • pp.579-585
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    • 2007
  • Formation of inclusion bodies is usually observed when foreign proteins are overexpressed in E. coli. The formation of inclusion bodies might be prevented by lowering the rate of protein synthesis, and appropriate regulation of the protein expression rate may lead to the soluble expression. In this study, human growth hormone (rhGH) was expressed in a soluble form by slowing down the protein synthesis rate, which was controlled in the transcriptional and translational levels. The transcriptional level was controlled by the regulation of the amount of RNA polymerase specific to the promoter in front of the rhGH gene. For lowering the rate of translation, the T7 transcription terminator-deleted vector was used to synthesize the longer mRNA of the target gene because the longer mRNA is expected to reduce the availability of tree ribosomes. In both methods, the percentage of soluble expression increased when the expression rate slowed down, and more than 93% of rhGH expressed was a soluble form in the T7 transcription terminator-deleted expression system.

여정자 추출물의 Tyrosinase 및 MITF 발현 억제 효과 (Inhibitory Effect of Fructus Ligustri Lucidi on Tyrosinase and MITF Expressions)

  • 한규수;김대성;우원홍;문연자
    • 동의생리병리학회지
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    • 제24권2호
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    • pp.296-301
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    • 2010
  • The purpose of this study was to investigate the mechanism of Hexane extract of Fructus Ligustri Lucidi (HFLL)-induced regulation of melanogenesis. An apparent down-regulatory effect of tyrosinase activity was observed when B16F10 cells were incubated with HFLL. Interestingly, HFLL did not inhibit the catalytic activity of cell-free tyrosinase from B16F10 cells, whereas kojic acid directly inhibited tyrosinase activity. Regarding protein levels of melanogenic enzymes, the amounts of tyrosinase and tyrosinase-related protein 1 (TRP-1) were decreased by HFLL, while the amount of tyrosinase-related protein 2 (TRP-2) slightly was reduced after incubation with HFLL. Treatment with HFLL was found to down-regulate microphthalmia-associated transcription factor (MITF). These results suggest that HFLL is an effective inhibitor of pigmentation caused by down regulation via MITF, tyrosinase, and TRP-1 expressions.

HIF-1α-Dependent Gene Expression Program During the Nucleic Acid-Triggered Antiviral Innate Immune Responses

  • Hong, Sun Woo;Yoo, Jae Wook;Kang, Hye Suk;Kim, Soyoun;Lee, Dong-ki
    • Molecules and Cells
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    • 제27권2호
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    • pp.243-250
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    • 2009
  • Recent studies suggest a novel role of $HIF-1{\alpha}$ under nonhypoxic conditions, including antibacterial and antiviral innate immune responses. However, the identity of the pathogen-associated molecular pattern which triggers $HIF-1{\alpha}$ activation during the antiviral response remains to be identified. Here, we demonstrate that cellular administration of double-stranded nucleic acids, the molecular mimics of viral genomes, results in the induction of $HIF-1{\alpha}$ protein level as well as the increase in $HIF-1{\alpha}$ target gene expression. Whole-genome DNA microarray analysis revealed that double-stranded nucleic acid treatment triggers induction of a number of hypoxia-inducible genes, and induction of these genes are compromised upon siRNA-mediated $HIF-1{\alpha}$ knock-down. Interestingly, $HIF-1{\alpha}$ knock-down also resulted in down-regulation of a number of genes involved in antiviral innate immune responses. Our study demonstrates that $HIF-1{\alpha}$ activation upon nucleic acid-triggered antiviral innate immune responses plays an important role in regulation of genes involved in not only hypoxic response, but also immune response.

Microarray Analysis of Gene Expression Profiles in Response to Treatment with Melatonin in Lipopolysaccharide Activated RAW 264.7 Cells

  • Ban, Ju-Yeon;Kim, Bum-Sik;Kim, Soo-Cheol;Kim, Dong-Hwan;Chung, Joo-Ho
    • The Korean Journal of Physiology and Pharmacology
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    • 제15권1호
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    • pp.23-29
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    • 2011
  • Melatonin, which is the main product of the pineal gland, has well documented antioxidant and immune-modulatory effects. Macrophages produce molecules that are known to play roles in inflammatory responses. We conducted microarray analysis to evaluate the global gene expression profiles in response to treatment with melatonin in lipopolysaccharide (LPS) activated RAW 264.7 macrophage cells. In addition, eight genes were subjected to real-time reverse transcription polymerase chain reaction (RT-PCR) to confirm the results of the microarray. The cells were treated with LPS or melatonin plus LPS for 24 hr. LPS induced the up-regulation of 1073 genes and the down-regulation of 1144 genes when compared to the control group. Melatonin pretreatment of LPS-stimulated RAW 264.7 cells resulted in the down regulation of 241 genes and up regulation of 164 genes. Interestingly, among genes related to macrophage-mediated immunity, LPS increased the expression of seven genes (Adora2b, Fcgr2b, Cish, Cxcl10, Clec4n, Il1a, and Il1b) and decreased the expression of one gene (Clec4a3). These changes in expression were attenuated by melatonin. Furthermore, the results of real-time PCR were similar to those of the microarray. Taken together, these results suggest that melatonin may have a suppressive effect on LPS-induced expression of genes involved in the regulation of immunity and defense in RAW 264.7 macrophage cells. Moreover, these results may explain beneficial effects of melatonin in the treatment of various inflammatory conditions.

Effect of ganglioside GD3 synthase gene expression on VSMC proliferation via ERK1/2 pathway, cell cycle progression and MMP-9 expression

  • Lee, Young-Choon;Kim, Cheorl-Ho
    • 한국식물생명공학회:학술대회논문집
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    • 한국식물생명공학회 2004년도 생명공학 실용화를 위한 비젼
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    • pp.81-90
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    • 2004
  • Sialic acid containing glycosphingolipids (gangliosides) have been implicated in the regulation of various biological phenomena such as atherosclerosis. Recent report suggeststhat exogenously supplied disialoganglioside (GD3) serves a dual role in vascular smooth muscle cells (VSMC) proliferation and apoptosis. However, the role of the GD3 synthase gene in VSMC responses has not yet been elucidated. To determine whether a ganglioside is able to modulate VSMC growth. the effect of overexpression of the GD3 synthase gene on DNA synthesis was examined. The results show that the overexpression of this gene has a potent inhibitory effect on DNA synthesis and ERK phosphorylation in cultured VSMC in the presence of PDGF. The suppression of the GD3 synthase gene was correlated with the down-regulation of cyclinE/CDK2. the up-regulation of the CDK inhibitor p21 and blocking of the p27 inhibition,whereas up-regulation of p53 as the result of GD3 synthase gene expression was not observed. Consistently, blockade of GD3 function with anti-GD3 antibody reversed VSMC proliferation and cell cycle proteins. The expression of the CD3 synthase gene also led to the inhibition of TNF--induced matrix metalloproteinase-9 (MMP-9) expression in VSMC as determined by zymography and immunoblot. Furthermore, GD3 synthase gene expression strongly decreased MMP-9 promoteractivlty in response to TNF-. This inhibition was characterized by the down-regulation of MMP-9,which was Iranscriptionally regulated at NF-B and activation protein-1 (AP-1) sites in the MMP-9promoter Finally, the overexpression of MMP-9 in GD3 synthase transfectant cells rescued VSMC proliferation. However MMP-2 overexpression was not affected the cell proliferation. These findings suggest that the fl13 synthase gene represents a physiological modulator of VSMC responses that may contribute to plaque instability in atherosclerosis.

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