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https://www.readbyqxmd.com/read/28439875/epigenetic-repression-of-mir-375-is-the-dominant-mechanism-for-constitutive-activation-of-the-pdpk1-rps6ka3-signalling-axis-in-multiple-myeloma
#1
Shotaro Tatekawa, Yoshiaki Chinen, Masaki Ri, Tomoko Narita, Yuji Shimura, Yayoi Matsumura-Kimoto, Taku Tsukamoto, Tsutomu Kobayashi, Eri Kawata, Nobuhiko Uoshima, Tomohiko Taki, Masafumi Taniwaki, Hiroshi Handa, Shinsuke Iida, Junya Kuroda
Cytogenetic/molecular heterogeneity is the hallmark of multiple myeloma (MM). However, we recently showed that the serine/threonine kinase PDPK1 and its substrate RPS6KA3 (also termed RSK2) are universally active in MM, and play pivotal roles in myeloma pathophysiology. In this study, we assessed involvement of aberrant miR-375 repression in PDPK1 overexpression in MM. An analysis of plasma cells from 30 pre-malignant monoclonal gammopathies of undetermined significance and 73 MM patients showed a significant decrease in miR-375 expression in patient-derived plasma cells regardless of the clinical stage, compared to normal plasma cells...
April 25, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28418019/live-imaging-of-h3k9-acetylation-in-plant-cells
#2
Kazuki Kurita, Takuya Sakamoto, Noriyoshi Yagi, Yuki Sakamoto, Akihiro Ito, Norikazu Nishino, Kaori Sako, Minoru Yoshida, Hiroshi Kimura, Motoaki Seki, Sachihiro Matsunaga
Proper regulation of histone acetylation is important in development and cellular responses to environmental stimuli. However, the dynamics of histone acetylation at the single-cell level remains poorly understood. Here we established a transgenic plant cell line to track histone H3 lysine 9 acetylation (H3K9ac) with a modification-specific intracellular antibody (mintbody). The H3K9ac-specific mintbody fused to the enhanced green fluorescent protein (H3K9ac-mintbody-GFP) was introduced into tobacco BY-2 cells...
April 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28416226/klotho-restoration-via-acetylation-of-peroxisome-proliferation-activated-receptor-%C3%AE-reduces-the-progression-of-chronic-kidney-disease
#3
Wenjun Lin, Qin Zhang, Lin Liu, Shasha Yin, Zhihong Liu, Wangsen Cao
Klotho is an anti-aging protein mainly expressed in the kidney. Reduced Klotho (1) expression closely correlates with the development and progression of chronic kidney disease (CKD). Klotho is also a downstream gene of Peroxisome Proliferation-Activated Receptor γ (PPARγ), a major transcription factor whose functions are significantly affected by post-translational modifications including acetylation. However, whether PPARγ acetylation regulates renal Klotho expression and function in CKD is unknown. Here we test whether renal damage and reduced Klotho expression in the adenine CKD mouse model can be attenuated by the pan histone deacetylase (HDAC) inhibitor trichostatin A...
April 14, 2017: Kidney International
https://www.readbyqxmd.com/read/28414324/correlation-between-histone-acetylation-and-expression-of-notch1-in-human-lung-carcinoma-and-its-possible-role-in-combined-small-cell-lung-carcinoma
#4
Wael Abdo Hassan, Shin-Ichiro Takebayashi, Mohamed Osama Ali Abdalla, Kosuke Fujino, Shinji Kudoh, Yamoto Motooka, Yonosuke Sato, Yoshiki Naito, Koichi Higaki, Joeji Wakimoto, Seiji Okada, Mituyoshi Nakao, Yuichi Ishikawa, Takaaki Ito
Combined small-cell lung carcinoma (cSCLC) is composed of small-cell lung carcinoma (SCLC) admixed with non-small-cell lung carcinoma (NSCLC). Evaluating the molecular differences between SCLC and NSCLC could lead to a better understanding of the pathogenesis of such neoplasms. Therefore, in this study, we investigated the correlation between histone acetylation and Notch1 expression in lung carcinoma. Using chromatin immunoprecipitation (ChIP) assay, we measured the level of acetylated histone H3 around the promoter region of Notch1 in SCLC and NSCLC cells...
April 17, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28412714/reprogramming-towards-totipotency-is-greatly-facilitated-by-synergistic-effects-of-small-molecules
#5
Kei Miyamoto, Yosuke Tajima, Koki Yoshida, Mami Oikawa, Rika Azuma, George E Allen, Tomomi Tsujikawa, Tomomasa Tsukaguchi, Charles R Bradshaw, Jerome Jullien, Kazuo Yamagata, Kazuya Matsumoto, Masayuki Anzai, Hiroshi Imai, John B Gurdon, Masayasu Yamada
Animal cloning has been achieved in many species by transplanting differentiated cell nuclei to unfertilized oocytes. However, the low efficiencies of cloning have remained an unresolved issue. Here we find that the combination of two small molecules, trichostatin A (TSA) and vitamin C (VC), under culture condition with bovine serum albumin deionized by ion-exchange resins, dramatically improves the cloning efficiency in mice and 15% of cloned embryos develop to term by means of somatic cell nuclear transfer (SCNT)...
April 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28406899/histone-deacetylase-inhibition-modulates-histone-acetylation-at-gene-promoter-regions-and-affects-genome-wide-gene-transcription-in-schistosoma-mansoni
#6
Letícia Anderson, Monete Rajão Gomes, Lucas Ferreira daSilva, Adriana da Silva Andrade Pereira, Marina M Mourão, Christophe Romier, Raymond Pierce, Sergio Verjovski-Almeida
BACKGROUND: Schistosomiasis is a parasitic disease infecting hundreds of millions of people worldwide. Treatment depends on a single drug, praziquantel, which kills the Schistosoma spp. parasite only at the adult stage. HDAC inhibitors (HDACi) such as Trichostatin A (TSA) induce parasite mortality in vitro (schistosomula and adult worms), however the downstream effects of histone hyperacetylation on the parasite are not known. METHODOLOGY/PRINCIPAL FINDINGS: TSA treatment of adult worms in vitro increased histone acetylation at H3K9ac and H3K14ac, which are transcription activation marks, not affecting the unrelated transcription repression mark H3K27me3...
April 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28387374/klotho-preservation-via-histone-deacetylase-inhibition-attenuates-chronic-kidney-disease-associated-bone-injury-in-mice
#7
Wenjun Lin, Yanning Li, Fang Chen, Shasha Yin, Zhihong Liu, Wangsen Cao
Bone loss and increased fracture are the devastating outcomes of chronic kidney disease-mineral and bone disorder (CKD-MBD) resulting from Klotho deficit-related mineral disturbance and hyperparathyroidism. Because Klotho down-regulation after renal injury is presumably affected by aberrant histone deacetylase (HDAC) activities, here we assess whether HDAC inhibition prevents Klotho loss and attenuates the CKD-associated bone complication in a mouse model of CKD-MBD. Mice fed adenine-containing diet developed the expected renal damage, a substantial Klotho loss and the deregulated key factors causally affecting bone remodeling, which were accompanied by a marked reduction of bone mineral density...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28384094/nuclear-survivin-promoted-by-acetylation-is-associated-with-the-aggressive-phenotype-of-oral-squamous-cell-carcinoma
#8
Shuli Liu, Lei Shi, Xi Yang, Dongxia Ye, Tong Wang, Cunshan Dong, Wenzheng Guo, Yueling Liao, Hongyong Song, Dongliang Xu, Jingzhou Hu, Zhiyuan Zhang, Jiong Deng
Defects in apoptotic pathway contribute to development and progression of oral cancer. Survivin, a member of the inhibitors of apoptosis protein (IAP) family, is increased in many types of cancers. However, it is unclear whether increased survivin is associated with oral squamous cell carcinomas (OSCC), and what mechanisms may involve in. In this study, we examined survivin expression in OSCC compared with normal oral tissues via immunohistochemical staining. The results showed that, not only total survivin is increased in OSCCs, but also the subcellular location of survivin is changed in OSCCs compared with normal oral tissues...
April 6, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28381181/effect-of-histone-modifications-on-hmlh1-alternative-splicing-in-gastric-cancer
#9
Jin-Xuan Zhao, Xiao-Wei Li, Bing-Yu Shi, Fang Wang, Zheng-Rong Xu, Hai-Lan Meng, Yun-Yan Su, Jing-Mei Wang, Nong Xiao, Qiong He, Ya-Ping Wang, Yi-Mei Fan
hMLH1 is one of the mismatch genes closely related to the occurrence of gastric cancer. Epigenetic regulation may play more important roles than gene mutations in DNA damage repair genes to drive carcinogenesis. In this article, we discuss the role of epigenetic changes, especially histone modifications in the regulation of hMLH1 alternative splicing. Our results showed that hMLH1 delEx10, delEx11, delEx10-11, delEx16 and delEx17 transcripts were ubiquitous in sporadic Chinese gastric cancer patients and gastric cancer cell lines...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28375564/effects-of-histone-deacetylase-inhibitors-on-regenerative-cell-responses-in-human-dental-pulp-cells
#10
Z Luo, Z Wang, X He, N Liu, B Liu, L Sun, J Wang, F Ma, H Duncan, W He, P Cooper
AIM: To investigate the growth, migratory and adhesive effects of Trichostatin A (TSA) and Valproic acid (VPA), two HDACis, on hDPSCs. METHODOLOGY: To verify that TSA or VPA functions as an HDAC inhibitor, the expressions of histone H3 and H4 were examined using Western blotting analysis. hDPSC growth and metabolic activity was evaluated by MTT viability analysis at different time-points and by cell count experiments. The expression of cell cycle regulatory and the apoptosis associated proteins were examined by Western blot analysis...
April 4, 2017: International Endodontic Journal
https://www.readbyqxmd.com/read/28356958/bioinformatic-identification-of-candidate-genes-induced-by-trichostatin-a-in-bgc-823-gastric-cancer-cells
#11
Yunlong Li, Lisha Zhang, Chunfa Yang, Riheng Li, Longbin Shang, Xiaoming Zou
The aim of the present study was to identify the candidate genes induced by trichostatin A (TSA) in BGC-823 gastric cancer (GC) cells and to explore the possible inhibition mechanism of TSA in GC. Gene expression data were obtained through chip detection, and differentially expressed genes (DEGs) between GC cells treated with TSA and untreated GC cells (control group) were identified. Gene ontology analysis of the DEGs was performed using the database for annotation, visualization and integrated discovery. Then sub-pathway enrichment analysis was performed and a microRNA (miRNA) regulatory network was constructed...
February 2017: Oncology Letters
https://www.readbyqxmd.com/read/28341057/histone-deacetylase-inhibitors-suppress-immature-dendritic-cell-s-migration-by-regulating-cc-chemokine-receptor-1-expression
#12
Young-Hoon Kim, Jae Kwon Lee
The modulation of immature dendritic cells (iDCs), which involves processes such as phagocytosis, migration, and maturation, is considered a beneficial research theme. Once activated by an antigen, iDCs turn to mature DCs (mDCs) and migrate towards secondary lymphoid organs, and initiate the progress of cellular immunity. Histone deacetylase inhibitors (HDACis) are also thought to be a major modulator of cellular immunity. Herein, we demonstrate that HDACis (trichostatin-A (TSA), sodium butylate (SB), scriptaid (ST)) play a central regulatory role in the migratory activity of iDCs...
February 28, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28323900/long-term-exposure-to-estrogen-enhances-chemotherapeutic-efficacy-potentially-through-epigenetic-mechanism-in-human-breast-cancer-cells
#13
Yu-Wei Chang, Kamaleshwar P Singh
Chemotherapy is the most common clinical option for treatment of breast cancer. However, the efficacy of chemotherapy depends on the age of breast cancer patients. Breast tissues are estrogen responsive and the levels of ovarian estrogen vary among the breast cancer patients primarily between pre- and post-menopausal age. Whether this age-dependent variation in estrogen levels influences the chemotherapeutic efficacy in breast cancer patients is not known. Therefore, the objective of this study was to evaluate the effects of natural estrogen 17 beta-estradiol (E2) on the efficacy of chemotherapeutic drugs in breast cancer cells...
2017: PloS One
https://www.readbyqxmd.com/read/28300163/in-vitro-drug-testing-based-on-contractile-activity-of-c2c12-cells-in-an-epigenetic-drug-model
#14
Kazushi Ikeda, Akira Ito, Ryusuke Imada, Masanori Sato, Yoshinori Kawabe, Masamichi Kamihira
Skeletal muscle tissue engineering holds great promise for pharmacological studies. Herein, we demonstrated an in vitro drug testing system using tissue-engineered skeletal muscle constructs. In response to epigenetic drugs, myotube differentiation of C2C12 myoblast cells was promoted in two-dimensional cell cultures, but the levels of contractile force generation of tissue-engineered skeletal muscle constructs prepared by three-dimensional cell cultures were not correlated with the levels of myotube differentiation in two-dimensional cell cultures...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28281974/silencing-of-atp4b-of-atpase-h-k-transporting-beta-subunit-by-intragenic-epigenetic-alteration-in-human-gastric-cancer-cells
#15
Shuye Lin, Bonan Lin, Xiaoyue Wang, Yuanming Pan, Qing Xu, Jin-Shen He, Wanghua Gong, Rui Xing, Yuqi He, Lihua Guo, Youyong Lu, Ji Ming Wang, Jiaqiang Huang
The ATPase H+/K+ Transporting Beta Subunit (ATP4B) encodes the β subunit of the gastric H+, K+-ATPase, which controls gastric acid secretion and is therefore a target for acid reduction. Downregulation of ATP4B was recently observed in human gastric cancer (GC) without known mechanisms. In the present study, we demonstrated that ATP4B expression was decreased in human GC tissues and cell lines associated with DNA hypermethylation and histone hypoacetylation of histone H3 lysine 9 at its intragenic region close to the transcriptional start site...
March 13, 2017: Oncology Research
https://www.readbyqxmd.com/read/28191472/suppression-of-excessive-histone-deacetylases-activity-in-diabetic-hearts-attenuates-myocardial-ischemia-reperfusion-injury-via-mitochondria-apoptosis-pathway
#16
Yang Wu, Yan Leng, Qingtao Meng, Rui Xue, Bo Zhao, Liying Zhan, Zhongyuan Xia
Background. Histone deacetylases (HDACs) play a pivotal role in signaling modification and gene transcriptional regulation that are essential for cardiovascular pathophysiology. Diabetic hearts with higher HDACs activity were more vulnerable to myocardial ischemia/reperfusion (MI/R) injury compared with nondiabetic hearts. We are curious about whether suppression of excessive HDACs activity in diabetic heart protects against MI/R injury. Methods. Diabetic rats were subjected to 45 min of ischemia, followed by 3 h of reperfusion...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28174211/overlapping-and-divergent-actions-of-structurally-distinct-histone-deacetylase-inhibitors-in-cardiac-fibroblasts
#17
Katherine B Schuetze, Matthew S Stratton, Weston W Blakeslee, Michael F Wempe, Florence F Wagner, Edward B Holson, Yin-Ming Kuo, Andrew J Andrews, Tonya M Gilbert, Jacob M Hooker, Timothy A McKinsey
Inhibitors of zinc-dependent histone deacetylases (HDACs) profoundly affect cellular function by altering gene expression via changes in nucleosomal histone tail acetylation. Historically, investigators have employed pan-HDAC inhibitors, such as the hydroxamate trichostatin A (TSA), which simultaneously targets members of each of the three zinc-dependent HDAC classes (classes I, II, and IV). More recently, class- and isoform-selective HDAC inhibitors have been developed, providing invaluable chemical biology probes for dissecting the roles of distinct HDACs in the control of various physiologic and pathophysiological processes...
April 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28160167/histone-deacetylase-inhibitors-vpa-and-tsa-induce-apoptosis-and-autophagy-in-pancreatic-cancer-cells
#18
Maria Saveria Gilardini Montani, Marisa Granato, Claudio Santoni, Paola Del Porto, Nicolò Merendino, Gabriella D'Orazi, Alberto Faggioni, Mara Cirone
PURPOSE: Histone deacetylase inhibitors (HDACi) are anti-neoplastic agents that are known to affect the growth of different cancer types, but their underlying mechanisms are still incompletely understood. Here, we compared the effects of two HDACi, i.e., Trichostatin A (TSA) and Valproic Acid (VPA), on the induction of cell death and autophagy in pancreatic cancer-derived cells that exhibit a high metastatic capacity and carry KRAS/p53 double mutations. METHODS: Cell viability and proliferation tests were carried out using Trypan blue dye exclusion, MTT and BrdU assays...
April 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28129645/epigenetic-alterations-of-gastrokine-1-gene-expression-in-gastric-cancer
#19
Filomena Altieri, Chiara Stella Di Stadio, Antonella Federico, Giuseppina Miselli, Maurizio De Palma, Emilia Rippa, Paolo Arcari
The gastrokine 1 (GKN1) protein is important for maintaining the physiological function of the gastric mucosa. GKN1 is down-regulated in gastric tumor tissues and derived cell lines and its over-expression in gastric cancer cells induces apoptosis, suggesting a possible role for the protein as a tumor suppressor. However, the mechanism by which GKN1 is inactivated in gastric cancer remains unknown. Here, we investigated the causes of GKN1 silencing to determine if epigenetic mechanisms such as histonic modification could contribute to its down-regulation...
March 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28123081/histone-deacetylase-inhibitors-protect-against-pyruvate-dehydrogenase-dysfunction-in-huntington-s-disease
#20
Luana Naia, Teresa Cunha-Oliveira, Joana Rodrigues, Tatiana R Rosenstock, Ana Oliveira, Márcio Ribeiro, Catarina Carmo, Sofia I Oliveira-Sousa, Ana I Duarte, Michael R Hayden, A Cristina Rego
Transcriptional deregulation and changes in mitochondrial bioenergetics, including pyruvate dehydrogenase (PDH) dysfunction, have been described in Huntington's disease (HD). We previously showed that histone deacetylase inhibitors (HDACi), trichostatin A and sodium butyrate (SB), ameliorate mitochondrial function in cells expressing mutant huntingtin. In this work we investigated the effect of HDACi on regulation of PDH activity in striatal cells derived from HD knock-in mice and YAC128 mice. Mutant cells exhibited decreased PDH activity and increased PDH E1alpha phosphorylation/inactivation, accompanied by enhanced protein levels of PDH kinases (PDK)1/3...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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