• Title/Summary/Keyword: HDAC4

Search Result 75, Processing Time 0.023 seconds

Induction of Fungal Secondary Metabolites by Co-Culture with Actinomycete Producing HDAC Inhibitor Trichostatins

  • Gwi Ja Hwang;Jongtae Roh;Sangkeun Son;Byeongsan Lee;Jun-Pil Jang;Jae-Seoun Hur;Young-Soo Hong;Jong Seog Ahn;Sung-Kyun Ko;Jae-Hyuk Jang
    • Journal of Microbiology and Biotechnology
    • /
    • v.33 no.11
    • /
    • pp.1437-1447
    • /
    • 2023
  • A recently bioinformatic analysis of genomic sequences of fungi indicated that fungi are able to produce more secondary metabolites than expected. Despite their potency, many biosynthetic pathways are silent in the absence of specific culture conditions or chemical cues. To access cryptic metabolism, 108 fungal strains isolated from various sites were cultured with or without Streptomyces sp. 13F051 which mainly produces trichostatin analogues, followed by comparison of metabolic profiles using LC-MS. Among the 108 fungal strains, 14 produced secondary metabolites that were not recognized or were scarcely produced in mono-cultivation. Of these two fungal strains, Myrmecridium schulzeri 15F098 and Scleroconidioma sphagnicola 15S058 produced four new compounds (1-4) along with a known compound (5), demonstrating that all four compounds were produced by physical interaction with Streptomyces sp. 13F051. Bioactivity evaluation indicated that compounds 3-5 impede migration of MDA-MB-231 breast cancer cells.

Trichostatin A, a Histone Deacetylase Inhibitor, Potentiated Cytotoxic Effect of ionizing Radiation in Human Head and Neck Cancer Cell Lines (히스톤탈아세틸효소 억제제 Trichostatin A에 의한 인간 두경부암 셰포주의 방사선 감수성 증강)

  • Kim, Jin Ho;Shin, Jin Hee;Chie, Eui Kyu;Wu, Hong-Gyun;Kim, Jae Sung;Kim, Il Han;Ha, Sung Whan;Park, Charn Il;Kang, Wee-Saing
    • Radiation Oncology Journal
    • /
    • v.22 no.2
    • /
    • pp.138-141
    • /
    • 2004
  • Purpose : We have previously reported that human glioblastoma cells are sensitized to radiation-induced death after their exposure to trichostatin A (TSA), a histone deacetylase inhibitor (HDAC-1), prior to the irradiation. We aimed to measure the magnitude of the radiosensitizing effect of TSA in human head and neck cancer cell lines. Materials and Methods : Human head and neck cancer cell lines, HN-3 and HN-9, were exposed to 0, 50, 100, and 200 nM TSA for 18 hr prior to irradiation. Then, the TSA-treated cells were irradiated with 0, 2, 4, 6, and 8 Gy, and cell survival was measured by clonogenic assay. Results : Pre-irradiation exposure to TSA was found to radiosensitize HN-3 and HN-9 cell lines. In HN-9 cells, the fraction surviving after 2 Gy (SF2) was significantly reduced by treatment of TSA at concentration as low as 50 nM. However, a treatment with 200 nM TSA was required to significantly decrease SF2 in the HN-3 cell line. SER of pre-irradiation treatment with 200 nM TSA was 1.84 in HN-3 and 7.24 in HN-9, respectively. Conclusions : Our results clearly showed that human head and neck cancer cell lines can be sensitized to ionizing radiation by pre-irradiation inhibition of histone deacetylase (HDAC) using TSA, and that this potentiation might well be a general phenomenon.

Effect of Reboxetine Pretreatment on the Forced Swimming Test-induced Gene Expression Profile in the Rat Lateral Septum

  • Moon, Bo-Hyun;Kang, Seung-Woo;Kim, Hyun-Ju;Shin, Seung-Keon;Choi, Sang-Hyun;Lee, Min-Soo;Kim, Myeung-Kon;Shin, Kyung-Ho
    • Molecular & Cellular Toxicology
    • /
    • v.4 no.1
    • /
    • pp.31-44
    • /
    • 2008
  • The forced swim test (FST) is the most widely used model for assessing potential antidepressant activity. Although it has been shown that lateral septum is involved with the FST-related behavior, it is not clear whether antidepressant treatments could alter the FST-induced gene expression profile in the lateral septum. In the present study, the gene expression profiles in response to FST and reboxetine pretreatment were observed in the lateral septum of rats. Reboxetine is known as a most selective serotonin norepinephrine reuptake inhibitor. In addition, we compared the changes in gene expression profile between reboxetine response and nonresponse groups, which were determined by counting FST-related behavior. After FST, lateral septum from controls and reboxetine pretreated group were dissected and gene expression profiles were assessed using an Affymetrix microarray system containing 15,923 genes. Various genes with different functions were changed in reboxetine response group compared with reboxetine nonresponse group, In particular, pleiotrophin, orexin receptor 2, serotonin 2A receptor, neuropeptide Y5 receptor and thyroid hormone receptor $\beta$ were decreased in reboxetine response group, but Lim motif-containing protein kinase 1 (Limk1) and histone deacetylase 1 (HDAC1) were increased. Although further studies are required for direct roles of these genes in reboxetine response, the microarray may provide tools to find out potential target genes and signaling pathways in antidepressant response.

Polymorphisms in Epigenetic and Meat Quality Related Genes in Fourteen Cattle Breeds and Association with Beef Quality and Carcass Traits

  • Liu, Xuan;Usman, Tahir;Wang, Yachun;Wang, Zezhao;Xu, Xianzhou;Wu, Meng;Zhang, Yi;Zhang, Xu;Li, Qiang;Liu, Lin;Shi, Wanhai;Qin, Chunhua;Geng, Fanjun;Wang, Congyong;Tan, Rui;Huang, Xixia;Liu, Airong;Wu, Hongjun;Tan, Shixin;Yu, Ying
    • Asian-Australasian Journal of Animal Sciences
    • /
    • v.28 no.4
    • /
    • pp.467-475
    • /
    • 2015
  • Improvement for carcass traits related to beef quality is the key concern in beef production. Recent reports found that epigenetics mediates the interaction of individuals with environment and nutrition. The present study was designed to analyze the genetic effect of single nucleotide polymorphisms (SNPs) in seven epigenetic-related genes (DNMT1, DNMT3a, DNMT3b, DNMT3L, Ago1, Ago2, and HDAC5) and two meat quality candidate genes (CAPN1 and PRKAG3) on fourteen carcass traits related to beef quality in a Snow Dragon beef population, and also to identify SNPs in a total of fourteen cattle populations. Sixteen SNPs were identified and genotyped in 383 individuals sampled from the 14 cattle breeds, which included 147 samples from the Snow Dragon beef population. Data analysis showed significant association of 8 SNPs within 4 genes related to carcass and/or meat quality traits in the beef populations. SNP1 (13154420A>G) in exon 17 of DNMT1 was significantly associated with rib-eye width and lean meat color score (p<0.05). A novel SNP (SNP4, 76198537A>G) of DNMT3a was significantly associated with six beef quality traits. Those individuals with the wild-type genotype AA of DNMT3a showed an increase in carcass weight, chilled carcass weight, flank thicknesses, chuck short rib thickness, chuck short rib score and in chuck flap weight in contrast to the GG genotype. Five out of six SNPs in DNMT3b gene were significantly associated with three beef quality traits. SNP15 (45219258C>T) in CAPN1 was significantly associated with chuck short rib thickness and lean meat color score (p<0.05). The significant effect of SNP15 on lean meat color score individually and in combination with each of other 14 SNPs qualify this SNP to be used as potential marker for improving the trait. In addition, the frequencies of most wild-type alleles were higher than those of the mutant alleles in the native and foreign cattle breeds. Seven SNPs were identified in the epigenetic-related genes. The SNP15 in CAPN1 could be used as a powerful genetic marker in selection programs for beef quality improvement in the Snow Dragon Beef population.

Effects of Early Life Stress on the Development of Depression and Epigenetic Mechanisms of p11 Gene (생애 초기 유해 경험이 우울증의 발병과 p11 유전자의 후성유전기전에 미치는 영향)

  • Seo, Mi Kyoung;Choi, Ah Jeong;Lee, Jung Goo;Urm, Sang-Hwa;Park, Sung Woo;Seog, Dae-Hyun
    • Journal of Life Science
    • /
    • v.29 no.9
    • /
    • pp.1002-1009
    • /
    • 2019
  • Early life stress (ELS) increases the risk of depression. ELS may be involved in the susceptibility to subsequent stress exposure during adulthood. We investigated whether epigenetic mechanisms of p11 promoter affect the vulnerability to chronic unpredictable stress (CUS) induced by the maternal separation (MS). Mice pups were separated from their dams (3 hr/day from P1-P21). When the pups reached adulthood, we applied CUS (daily for 3 weeks). The levels of hippocampal p11 expression were analyzed by quantitative real-time PCR. The levels of acetylated and methylated histone H3 at p11 promoter were measured by chromatin immunoprecipitation. Depression-like behavior was measured by the forced swimming test (FST). The MS and CUS group exhibited significant decreases in p11 mRNA level and the MS plus CUS group had a greater reduction in this level than the CUS group. The MS plus CUS group also resulted in greater reduction in H3 acetylation than the CUS group. This reduction was associated with an upregulation of histone deacetylase 5. Additionally, the MS plus CUS group showed a greater decrease in H3K4met3 level and a greater increase in H3K27 met3 level than the CUS group. Consistent with the reduction of p11 expression, the MS plus CUS group displayed longer immobility times in the FST compared to the control group. Mice exposed to MS followed by CUS had much greater epigenetic alterations in the hippocampus compared to adult mice that only experienced CUS. ELS can exacerbate the effect of stress exposure during adulthood through histone modification of p11 gene.