• Title/Summary/Keyword: RAB

Search Result 74, Processing Time 0.028 seconds

Proteomic Analysis and the Antimetastatic Effect of N-(4methyl)phenyl-O-(4-methoxy) phenyl-thionocarbamate-Induced Apoptosis in Human Melanoma SK-MEL-28 cells

  • Choi Su-La;Choi Yun-Sil;Kim Young-Kwan;Sung Nack-Do;Kho Chang-Won;Park Byong-Chul;Kim Eun-Mi;Lee Jung-Hyung;Kim Kyung-Mee;Kim Min-Yung;Myung Pyung-Keun
    • Archives of Pharmacal Research
    • /
    • v.29 no.3
    • /
    • pp.224-234
    • /
    • 2006
  • We employed human SK-MEL-28 cells as a model system to identify cellular proteins that accompany N-(4-methyl)phenyl-O-(4-methoxy)phenyl-thionocarbamate (MMTC)-induced apoptosis based on a proteomic approach. Cell viability tests revealed that SK-MEL-28 skin cancer cells underwent more cell death than normal HaCaT cells in a dose-dependent manner after treatment with MMTC. Two-dimensional electrophoresis in conjunction with matrixassisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry analysis or computer matching with a protein database further revealed that the MMTC-induced apoptosis is accompanied by increased levels of caspase-1, checkpoint suppressor-1, caspase-4, NF-kB inhibitor, AP-2, c-Jun-N-terminal kinase, melanoma inhibitor, granzyme K, G1/S specific cyclin D3, cystein rich protein, Ras-related protein Rab-37 or Ras-related protein Rab-13, and reduced levels of EMS (oncogene), ATP synthase, tyrosine-phosphatase, Cdc25c, 14-3-3 protein or specific structure of nuclear receptor. The migration suppressing effect of MMTC on SK-MEL-28 cell was tested. MMTC suppressed the metastasis of SK-MEL-8 cells. It was also identified that MMTC had little angiogenic effect because it did not suppress the proliferation of HUVEC cell line. These results suggest that MMTC is a novel chemotherapeutic and metastatic agents against the SK-MEL-28 human melanoma cell line.

Inhibitory Effects of Novel Hexapeptide on Melanogenesis by Regulating MITF in B16F10 Melanoma Cells (B16F10 멜라닌 세포에서 신규 헥사펩타이드의 MITF 조절을 통한 멜라닌 생성 저해 효과)

  • Lee, Eung Ji;Kim, Jandi;Jeong, Min Kyeong;Lee, Young Min;Chung, Yong Ji;Kim, Eun Mi
    • Journal of the Society of Cosmetic Scientists of Korea
    • /
    • v.46 no.1
    • /
    • pp.11-22
    • /
    • 2020
  • In this study, we investigated anti-pigmentation effect of a hexapeptide. The peptide significantly reduced melanin contents and inhibited tyrosinase activity in a dose-dependent manner, in which tyrosinase is a key enzyme in melanogenesis. The peptide also significantly reduced the expression levels of tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1) and their upstream transcription factor, microphthalmia-associated transcription factor (MITF). Furthermore, the peptide suppressed the phosphorylation level of cAMP-response element binding protein (CREB), a transcription factor of MITF, and increased the phosphorylation level of extracellular signal-regulated kinase (ERK), a kinase mediates MITF phosphorylation and proteasomal degradation. The peptide significantly inhibited the expression of Rab27A, Melanophilin, and MyosinVa, the components of motor complex involved in intracellular movement of melanosome. These results suggest that Hexapeptide could be used as an effective whitening agent that has inhibitory effect on melanin production and melanosome transport by regulating expression and degradation of MITF in melanocytes.

Mon1 Is Essential for Fungal Virulence and Stress Survival in Cryptococcus neoformans

  • Son, Ye-Eun;Jung, Won-Hee;Oh, Sang-Hun;Kwak, Jin-Hwan;Cardenas, Maria E.;Park, Hee-Soo
    • Mycobiology
    • /
    • v.46 no.2
    • /
    • pp.114-121
    • /
    • 2018
  • Mon1 is a guanine nucleotide exchange factor subunit that activates the Ypt7 Rab GTPase and is essential for vacuole trafficking and autophagy in eukaryotic organisms. Here, we identified and characterized the function of Mon1, an ortholog of Saccharomyces cerevisiae Mon1, in a human fungal pathogen, Cryptococcus neoformans. Mutation in mon1 resulted in hypersensitivity to thermal stress. The mon1 deletion mutant exhibited increased sensitivity to cell wall and endoplasmic reticulum stress. However, the mon1 deletion mutant showed more resistance to the antifungal agent fluconazole. In vivo studies demonstrated that compared to the wild-type strain, the mon1 deletion mutant attenuated virulence in the Galleria mellonella insect model. Moreover, the mon1 deletion mutant was avirulent in the murine inhalation model. These results demonstrate that Mon1 plays a crucial role in stress survival and pathogenicity in C. neoformans.

Molecular characterizations of phosphoprotein of rabies virus circulating in Korea

  • Kim, Ha-Hyun;Yang, Dong-Kun;Jeon, Jeong Kuk;Cho, Soo-Dong;Song, Jae-Young
    • Korean Journal of Veterinary Research
    • /
    • v.52 no.1
    • /
    • pp.9-18
    • /
    • 2012
  • Rabies is a major zoonotic disease that causes approximately 55,000 human deaths worldwide on an annual basis. The nucleocapsid protein and glycoprotein genes of the Korean rabies virus (RABV) have been subjected to molecular and phylogenetic analyses. Although the phosphoprotein (P) has several important functions in viral infection and pathogenicity, the genetic characterizations of the P of Korean RABV isolates have not yet been established. In the present study, we conducted genetic analyses of P genes of 24 RABV isolates circulating in the Republic of Korea (hereafter, Korea) from 2008 to 2011. This study revealed that the P genes of Korean RABVs are genetically similar to those of RABV strains of lyssavirus genotype I including V739 (dogs, Korea), NNV-RAB-H (humans, India), NeiMeng925 (raccoon dogs, China), and RU9.RD (raccoon dogs, Russia). Among Korean isolates, the RABV P genes showed low variability in the variable domains among Korean isolates; they had specific consensus sequences and amino acid substitutions capable of identifying geographic characteristics and retained specific sequences thought to be important for viral function. These results provide important genetic characteristics and epidemiological information pertaining to the P gene of the Korean RABV.

A Genome-wide Scan for Selective Sweeps in Racing Horses

  • Moon, Sunjin;Lee, Jin Woo;Shin, Donghyun;Shin, Kwang-Yun;Kim, Jun;Choi, Ik-Young;Kim, Jaemin;Kim, Heebal
    • Asian-Australasian Journal of Animal Sciences
    • /
    • v.28 no.11
    • /
    • pp.1525-1531
    • /
    • 2015
  • Using next-generation sequencing, we conducted a genome-wide scan of selective sweeps associated with selection toward genetic improvement in Thoroughbreds. We investigated potential phenotypic consequence of putative candidate loci by candidate gene association mapping for the finishing time in 240 Thoroughbred horses. We found a significant association with the trait for Ral GApase alpha 2 (RALGAP2) that regulates a variety of cellular processes of signal trafficking. Neighboring genes around RALGAP2 included insulinoma-associated 1 (INSM1), pallid (PLDN), and Ras and Rab interactor 2 (RIN2) genes have similar roles in signal trafficking, suggesting that a co-evolving gene cluster located on the chromosome 22 is under strong artificial selection in racehorses.

Roles of Oxidative Stress in the Development and Progression of Breast Cancer

  • Nourazarian, Ali Reza;Kangari, Parisa;Salmaninejad, Arash
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.12
    • /
    • pp.4745-4751
    • /
    • 2014
  • Oxidative stress is caused by an imbalance in the redox status of the body. In such a state, increase of free radicals in the body can lead to tissue damage. One of the most important species of free radicals is reactive oxygen species (ROS) produced by various metabolic pathways, including aerobic metabolism in the mitochondrial respiratory chain. It plays a critical role in the initiation and progression of various types of cancers. ROS affects different signaling pathways, including growth factors and mitogenic pathways, and controls many cellular processes, including cell proliferation, and thus stimulates the uncontrolled growth of cells which encourages the development of tumors and begins the process of carcinogenesis. Increased oxidative stress caused by reactive species can reduce the body's antioxidant defense against angiogenesis and metastasis in cancer cells. These processes are main factors in the development of cancer. Bimolecular reactions cause free radicals in which create such compounds as malondialdehyde (MDA) and hydroxyguanosine. These substances can be used as indicators of cancer. In this review, free radicals as oxidizing agents, antioxidants as the immune system, and the role of oxidative stress in cancer, particularly breast cancer, have been investigated in the hope that better identification of the factors involved in the occurrence and spread of cancer will improve the identification of treatment goals.

Gene Expression Analysis of Hepatic Response Induced by Gentamicin in Mice

  • Oh, Jung-Hwa;Park, Han-Jin;Hwang, Ji-Yoon;Jeong, Sun-Young;Lim, Jung-Sun;Kim, Yong-Bum;Yoon, Seok-Joo
    • Molecular & Cellular Toxicology
    • /
    • v.3 no.1
    • /
    • pp.60-67
    • /
    • 2007
  • Gentamicin is a broad-spectrum aminoglycoside antibiotic used in the treatment of bacterial infection. Although side effects of gentamicin such as nephrotoxicity and ototoxicity have been investigated, the information on the hepatic effects of gentamicin is still limited. In the present study, gene expression profiles were analyzed in the liver of gentamicin treated mice using Affymetrix GeneChip$^{(R)}$ Mouse Expression 430A 2.0 Array. Totally, 400 genes were identified as being either up- or down-regulated over 1.5-fold changes (P<0.01) in the liver of gentamicin treated mice. Among these deregulated genes, 16 up-regulated genes mainly involved in transport (Kif5b, Pex14, Rab14, Clcn3, and Necap1) and 20 down-regulated genes involved in lipid and other metabolisms (Hdlbp, Gm2a, Uroc1, and Dak) were selected using k-means clustering algorithm. The functional classification of differentially expressed genes represented that several stress-related genes were regulated in the liver by gentamicin treatment. This data may contribute in understanding the molecular mechanism in the liver of gentamicin treated mice.

Identification of Differentially Expressed Genes by TCDD in Human Bronchial Cells: Toxicogenomic Markers for Dioxin Exposure

  • Park, Chung-Mu;Jin, Kyong-Suk;Lee, Yong-Woo
    • Biomedical Science Letters
    • /
    • v.18 no.1
    • /
    • pp.1-9
    • /
    • 2012
  • Differentially expressed genes by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were identified in order to evaluate them as dioxin-sensitive markers and crucial signaling molecules to understand dioxin-induced toxic mechanisms in human bronchial cells. Gene expression profiling was analyzed by cDNA microarray and ten genes were selected for further study. They were cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1), S100 calcium binding protein A8 (calgranulin A), S100 calcium binding protein A9 (calgranulin B), aldehyde dehydrogenase 1 family, member A3 (ALDH6) and peroxiredoxin 5 (PRDX5) in up-regulated group. Among them, CYP1B1 was used as a hallmark for dioxin and sharply increased by TCDD exposure. Down-regulated genes were IK cytokine, interferon-induced protein with tetratricopeptide repeats 1 (IFIT1), nuclease sensitive element binding protein 1 (NSEP1), protein tyrosine phosphatase type VI A, member 1 (PTP4A1), ras oncogene family 32 (RAB32). Although up-regulated 4 genes in microarray were coincided with northern hybridization, down-regulated 5 genes showed U-shaped expression pattern which is sharply decreased at lower doses and gradually increased at higher doses. These results introduce some of TCDD-responsive genes can be sensitive markers against TCDD exposure and used as signaling cues to understand toxicity initiated by TCDD inhalation in pulmonary tissues.

Mass Spectrometry-Based Screening Platform Reveals Orco Interactome in Drosophila melanogaster

  • Yu, Kate E.;Kim, Do-Hyoung;Kim, Yong-In;Jones, Walton D.;Lee, J. Eugene
    • Molecules and Cells
    • /
    • v.41 no.2
    • /
    • pp.150-159
    • /
    • 2018
  • Animals use their odorant receptors to receive chemical information from the environment. Insect odorant receptors differ from the G protein-coupled odorant receptors in vertebrates and nematodes, and very little is known about their protein-protein interactions. Here, we introduce a mass spectrometric platform designed for the large-scale analysis of insect odorant receptor protein-protein interactions. Using this platform, we obtained the first Orco interactome from Drosophila melanogaster. From a total of 1,186 identified proteins, we narrowed the interaction candidates to 226, of which only two-thirds have been named. These candidates include the known olfactory proteins Or92a and Obp51a. Around 90% of the proteins having published names likely function inside the cell, and nearly half of these intracellular proteins are associated with the endomembrane system. In a basic loss-of-function electrophysiological screen, we found that the disruption of eight (i.e., Rab5, CG32795, Mpcp, Tom70, Vir-1, CG30427, Eaat1, and CG2781) of 28 randomly selected candidates affects olfactory responses in vivo. Thus, because this Orco interactome includes physiologically meaningful candidates, we anticipate that our platform will help guide further research on the molecular mechanisms of the insect odorant receptor family.

The Mediating Effect of Dementia Recognition on the Number of Chronic Diseases and Dementia Prevention Behaviors of Elders in Rural Communities (농촌 지역사회노인의 만성질병수와 치매예방행위에 미치는 치매인식의 매개효과)

  • Park, Pilnam
    • Journal of Korean Academy of Rural Health Nursing
    • /
    • v.15 no.2
    • /
    • pp.41-48
    • /
    • 2020
  • Purpose: This study was a descriptive study to identify the factors affecting the dementia prevention behavior of elders in rural communities. Methods: The participants in this study were 125 elders aged 60 or older who lived in Eup or Myeon areas of P city. For data analysis, SPSS/WIN 22.0 was used to perform descriptive statistics, t-test, ANOVA, Pearson correlation, and linear multiple regression and mediated effects. Results: Scores for dementia recognition, dementia attitude and dementia prevention behavior averaged 5.6±2.50 points in the 0~11 range, 38.8±4.59 in 14~56 and 20.2±3.59 in 10~30 respectively. Dementia recognition (a), dementia attitude (b), dementia prevention behavior (c) and the number of chronic diseases of the elders (d) were positively or negatively correlated with each other (rab=.29, p<.01; rbc=.26, p<.01; rac=.36, p<.01; rad=-.29, p<.01; rcd=.19, p<.05). Factors affecting dementia prevention behavior were dementia recognition, dementia attitude, and degree of dementia interest. When the number of chronic diseases affects dementia prevention behavior, dementia recognition has a mediating effect. Conclusion: In order to prevent dementia among elders in rural areas, appropriate management of chronic diseases and provision of appropriate dementia-related education and information to enhance dementia recognition should be provided.