• Title/Summary/Keyword: protein-protein interactions network

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Effects of Thujae Orientalis Folium (TOF) on Gene Expression of Human melanoma cells (SK-MEL-2) (측백엽(側柏葉)이 인간 유래 악성 흑색종 세포의 유전자 발현에 미치는 영향)

  • Jung, Min-Young;Kim, Jong-Han;Park, Su-Yeon;Choi, Jeong-Hwa
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.23 no.2
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    • pp.81-108
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    • 2010
  • Objective : Thujae Orientalis Folium (TOF) can cool the blood and stop bleeding, eliminate phlegm and relieve cough in Oriental medicine. In addition, the fresh is used alone externally. Recently, TOF is known to have anti-tumor component. And also known to have tyrosinase inhibitory effect. Method : For these reasons, this study was designed to investigate anti-cancer and whitening activities of TOF. In this experiment, effects of TOF on proliferation rates of melanoma cells and on changes in genetic profiles were investigated. The genetic profile for the effect on human derived melanoma cell, SK-MEL-2, was measured using microarray technique, and the functional analysis on these genes was conducted. Results : Total 541 genes were up-regulated and 1,079 genes down-regulated in cells treated with TOF. Genes induced by TOF were mainly concerned with anti-cancer effects and apoptosis. Genes suppresed by TOF were related in extracellular signalling pathway. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as THAP1, MAX1, STAM2, SMAD6, CYCS, PEX5, PSEN1, NONO, MAP2K7 and CREB1 that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conculusion : These results suggest possibility of TOF as anti-cancer drug for human melanoma. In addition, the present author also suggest that related mechanisms are involved in inhibition of several cancer pathway, activation of apoptosis pathway and suppression of general metabolic pathway.

Effects of Gleditsiae Spina(GS) on the Polycystic Ovary Induced by Estradiol Valerate in Rats (조각자(皂角刺)가 estradiol valerate로 유발된 백서(白鼠)의 다낭성 난소에 미치는 영향)

  • Gu, Hee-Jun;Cho, Sung-Hee
    • The Journal of Korean Obstetrics and Gynecology
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    • v.23 no.2
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    • pp.71-84
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    • 2010
  • Purpose: In the theory of traditional medicine, Glenditsia spina(GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. This study was designed to investigate the effects of GS on gene expression of ovarian tissue in polycystic ovary syndrome(PCOS) rats. Methods: In this experiment, female rats injected with a single dose of 2 mg estradiol valerate(EV) and GS was given for 5 weeks. The genetic profile for the effects on ovarian tissue in PCOS rats was measured using microarray technique, and the functional analysis on these genes was conducted. Results: 985 genes were increased in control and restored to normal level in GS group. (B), 733 genes were decreased in control group and restored to normal level in GS group. (F). Metabolic pathways related in B group genes were Graft-versus-host disease, Allograft rejection, Autoimmune thyroid disease, Cytokine-cytokine receptor interaction, Small cell lung cancer, Type I diabetes mellitus. Metabolic pathways related in F group genes were Antigen processing and present, Adipocytokine signalling pathway, Focal adhesion, ECM-receptor interaction, Pancreatic cancer, Notch signalling pathway, Tight junction. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as c-Fos, c-Myc, ABL1 related in B group, MAPK8, RASA1, CALR related in F group that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: These results suggest possibility of GS as anti-cancer and anti-hyperplasia drug in PCOS. In addition, the present author also suggests that related mechanisms are involved in suppression of proto-oncogene such as c-Fos, c-Myc and ABL1, and in regulation of cell cycle such as RASA1.

Differentially Expressed Genes in Period 2-Overexpressing Mice Striatum May Underlie Their Lower Sensitivity to Methamphetamine Addiction-Like Behavior

  • Sayson, Leandro Val;Kim, Mikyung;Jeon, Se Jin;Custodio, Raly James Perez;Lee, Hyun Jun;Ortiz, Darlene Mae;Cheong, Jae Hoon;Kim, Hee Jin
    • Biomolecules & Therapeutics
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    • v.30 no.3
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    • pp.238-245
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    • 2022
  • Previous reports have demonstrated that genetic mechanisms greatly mediate responses to drugs of abuse, including methamphetamine (METH). The circadian gene Period 2 (Per2) has been previously associated with differential responses towards METH in mice. While the behavioral consequences of eliminating Per2 have been illustrated previously, Per2 overexpression has not yet been comprehensively described; although, Per2-overexpressing (Per2 OE) mice previously showed reduced sensitivity towards METH-induced addiction-like behaviors. To further elucidate this distinct behavior of Per2 OE mice to METH, we identified possible candidate biomarkers by determining striatal differentially expressed genes (DEGs) in both drug-naïve and METH-treated Per2 OE mice relative to wild-type (WT), through RNA sequencing. Of the several DEGs in drug naïve Per2 OE mice, we identified six genes that were altered after repeated METH treatment in WT mice, but not in Per2 OE mice. These results, validated by quantitative real-time polymerase chain reaction, could suggest that the identified DEGs might underlie the previously reported weaker METH-induced responses of Per2 OE mice compared to WT. Gene network analysis also revealed that Asic3, Hba-a1, and Rnf17 are possibly associated with Per2 through physical interactions and predicted correlations, and might potentially participate in addiction. Inhibiting the functional protein of Asic3 prior to METH administration resulted in the partial reduction of METH-induced conditioned place preference in WT mice, supporting a possible involvement of Asic3 in METH-induced reward. Although encouraging further investigations, our findings suggest that these DEGs, including Asic3, may play significant roles in the lower sensitivity of Per2 OE mice to METH.

CD40-CD40 Ligand Interactions in the Production of IL-12 and IFN-γ by Tuberculous Pleural Mononuclear Cells

  • Song, Chang-Hwa;Nam, Hyun-Hee;An, Jeun-Ok;Lee, Ji-Sook;Kim, Hwa-Jung;Park, Jeong-Kyu;Suhr, Ji-Won;Jung, Sung-Soo;Na, Moon-Jun;Paik, Tae-Hyun;Jo, Eun-Kyeong
    • IMMUNE NETWORK
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    • v.2 no.3
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    • pp.142-149
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    • 2002
  • Background: Our previous study showed that purified protein derivative (PPD)-stimulated pleural mononuclear cells (PMC) from tuberculous pleurisy (Tbp) produced significantly more $IFN-{\gamma}$ (10- to 70-fold) after in vitro PPD stimulation than freshly isolated pleural cells from malignant pleurisy. The present study was designed to determine whether blocking the CD40-CD40 ligand (CD40L) interaction decreases $IFN-{\gamma}$ production by altering IL-12 levels. Methods: IL-12 and $IFN-{\gamma}$ production after neutralizing anti-CD40L antibody treatment was compared to the efficacy of anti-CD80, anti-CD86, and a combination of anti-CD80 and CD86 (CD80+86) monoclonal antibodies (mAb). These activities were measured by enzyme-linked immunosorbent assays (ELISAs) and reverse transcription-polymerase chain reaction (RT-PCR), after in vitro stimulation with PPO antigen (Ag). Results: Neutralization of CD80, CD86 and CD80+86 did not decrease $IFN-{\gamma}$ and IL-12 production in Tbp-PMC, whereas neutralization of CD40L significantly depressed IL-12 p40 and $IFN-{\gamma}$. In addition, neutralization of CD40L completely inhibited IL-12 p40 and $IFN-{\gamma}$ mRNA expression. Conclusion: The CD40-CD40L interaction might play a major role in IL-12 and $IFN-{\gamma}$ production in Tbp-PMC, thus contributing to protective immunity in human tuberculosis.

Effects of Angelicae Gigantis Radix on Gene Expression of Ovarian Tissue in Polycystic Ovary Syndrome Rats (당귀(當歸)가 다낭성난소증후군이 유발된 흰쥐 난소조직의 유전자 발현에 미치는 영향)

  • Ryu, Ki-Jun;Cho, Sung-Hee
    • The Journal of Korean Obstetrics and Gynecology
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    • v.24 no.3
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    • pp.28-47
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    • 2011
  • Objectives: This study was performed to investigate the effects of Angelicae gigantis Radix (AGR) which is one of the most useful herbal-drug to treat patients with Polycystic Ovary Syndrome (PCOS) in Oriental medicine on gene expression of ovary tissue. Methods: The effects of AGR on gene expression of ovary tissue resected from PCOS induced rats using single injection of $\ss$-Estradiol 17-valerate (EV) was measured using microarray technique, and the functional analysis on these genes was conducted. Results: Total 2,812 genes were up-regulated or down-regulated, 1,421 genes were up-regulated, 1,391 genes were down-regulated by induction of PCOS. Up-regulated genes were mainly involved in biological function such as cell signalling pathways and inflammatory response. Expression levels of 1,442 genes were restored to those of naive animals by administration of AGR. 558 genes were restored to those of naive animals, which were lowered by induction of PCOS. 884 genes were lowered to naive levels, which were elevated by induction of PCOS. The functions of restored genes were partially involved in the restoration of expression levels, which were changed by induction of PCOS. Especially, up-regulated gene by induction of PCOS were mainly involved in these changes. These results mean restorative effects of AGR on damaged functions by induction of PCOS. The network of total protein interactions was measured using cytoscape program, and some key molecules, such as IRS2, MCM10, ORC2L related in up-regulated genes, CTBP2, CD44, RHOA, related in down-regulated genes that can be used for elucidation of therapeutical mechanism of medicine in future were identified. Conclusion: Restored genes by AGR were thought to have common pathways related in regulation of gene expressions. Especially, genes in restored expression levels by AGR, which were up-regulated by induction of PCOS, were regulated by 9 of common transcription factors, genes in restored expression levels by AGR, which were down-regulated by induction of PCOS, were involved in 25 of common transcription factors.