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https://www.readbyqxmd.com/read/28720877/role-of-the-histone-deacetylase-inhibitor-valproic-acid-in-high-fat-diet-induced-hypertension-via-inhibition-of-hdac1-angiotensin-ii-axis
#1
J Choi, S Y Park, T K Kwon, S-I Sohn, K M Park, J I Kim
BACKGROUND: Obesity is known as an epidemic worldwide because of consumption of westernized high-fat diets and one of the major risk factors of hypertension. Histone deacetylases (HDACs) control gene expression by regulating histone/non-histone protein deacetylation. HDAC inhibitors exert anti-cancer and anti-inflammatory effects and play a protective role in cardiovascular diseases. In the present study, we tested the effect of an FDA-approved pan-HDAC inhibitor valproic acid (VPA) on high-fat diet (HFD)-induced hypertension in mice...
July 19, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28713892/trichostatin%C3%A2-a-induces-bladder-cancer-cell-death-via-intrinsic-apoptosis-at-the-early%C3%A2-phase-and-sp1%C3%A2-survivin-downregulation-at-the-late%C3%A2-phase-of-treatment
#2
Shou-Chieh Wang, Shou-Tsung Wang, Hung-Te Liu, Xiang-Yu Wang, She-Ching Wu, Lei-Chin Chen, Yi-Wen Liu
Histone deacetylase (HDAC) inhibitors have been widely shown to result in cancer cell death. The present study investigated the mechanisms underlying the antitumor effects of the phytochemical trichostatin A (TSA), a classic pan-HDAC inhibitor, in 5,637 urinary bladder cancer cells. It was found that TSA caused cell cycle arrest at the G2/M and G1 phase accompanied by reduced expression of cyclin D1 and upregulated induction of p21. In addition, TSA induced morphological changes, reduced cell viability and apoptotic cell death in 5,637 cells through caspase-3 activation followed by PARP cleavage...
July 6, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28701956/administration-of-a-histone-deacetylase-inhibitor-into-the-basolateral-amygdala-enhances-memory-consolidation-delays-extinction-and-increases-hippocampal-bdnf-levels
#3
Fernanda E Valiati, Mailton Vasconcelos, Martina Lichtenfels, Fernanda S Petry, Rosa M M de Almeida, Gilberto Schwartsmann, Nadja Schröder, Caroline B de Farias, Rafael Roesler
Gene expression related to the formation and modification of memories is regulated epigenetically by chromatin remodeling through histone acetylation. Memory formation and extinction can be enhanced by treatment with inhibitors of histone deacetylases (HDACs). The basolateral amygdala (BLA) is a brain area critically involved in regulating memory for inhibitory avoidance (IA). However, previous studies have not examined the effects of HDAC inhibition in the amygdala on memory for IA. Here we show that infusion of an HDAC inhibitor (HDACi), trichostatin A (TSA), into the BLA, enhanced consolidation of IA memory in rats when given at 1...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28700937/%C3%AE-fosb-regulates-gene-expression-and-cognitive-dysfunction-in-a-mouse-model-of-alzheimer-s-disease
#4
Brian F Corbett, Jason C You, Xiaohong Zhang, Mark S Pyfer, Umberto Tosi, Daniel M Iascone, Iraklis Petrof, Anupam Hazra, Chia-Hsuan Fu, Gabriel S Stephens, Annie A Ashok, Suzan Aschmies, Lijuan Zhao, Eric J Nestler, Jeannie Chin
Alzheimer's disease (AD) is characterized by cognitive decline and 5- to 10-fold increased seizure incidence. How seizures contribute to cognitive decline in AD or other disorders is unclear. We show that spontaneous seizures increase expression of ΔFosB, a highly stable Fos-family transcription factor, in the hippocampus of an AD mouse model. ΔFosB suppressed expression of the immediate early gene c-Fos, which is critical for plasticity and cognition, by binding its promoter and triggering histone deacetylation...
July 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28690765/novel-therapeutic-effects-of-leonurine-on-ischemic-stroke-new-mechanisms-of-bbb-integrity
#5
Qiu-Yan Zhang, Zhi-Jun Wang, De-Miao Sun, Ying Wang, Peng Xu, Wei-Jun Wu, Xin-Hua Liu, Yi-Zhun Zhu
Stroke is a leading cause of morbidity and mortality globally. Leonurine (also named SCM-198), a compound extracted from Herba leonuri, was effective on the prevention of various cardiovascular and brain diseases. The purpose of this study was to explore the possible therapeutic potential of SCM-198 against ischemia reperfusion injury and underlying mechanisms. In the in vivo transient middle cerebral artery occlusion (tMCAO) rat model, we found that treatment with SCM-198 could decrease infarct volume and improve neurological deficit by protecting against blood-brain barrier (BBB) breakdown...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28688716/exercise-induced-glut4-transcription-via-inactivation-of-hdac4-5-in-mouse-skeletal-muscle-in-an-ampk%C3%AE-2-dependent-manner
#6
Yanmei Niu, Tianyi Wang, Sujuan Liu, Hairui Yuan, Huige Li, Li Fu
Abnormal glucose metabolism induces various metabolic disorders such as insulin resistance and type 2 diabetes. Regular exercise improved glucose uptake and enhanced glucose oxidation by increasing GLUT4 transcription in skeletal muscle. However, the regulatory mechanisms of GLUT4 transcription in response to exercise are poorly understood. AMPK is a sensor of exercise and upstream kinase of class II HDACs that act as transcriptional repressors. We used 6-week treadmill exercise or one single-bout exercise wild type or AMPKα2(-/-) C57BL/6J mice to explore how HDACs regulate GLUT4 transcription and the underlying molecular mechanisms mediated by AMPK in the physiologic process of exercise...
July 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28685689/arylurea-derivatives-a-class-of-potential-cancer-targeting-agents
#7
Jia-Nian Chen, De-Wen Wu, Ting Li, Kang-Jian Yang, Li Cheng, Zu-Ping Zhou, Shi-Ming Pu, Wan-Hua Lin
Arylurea derivatives, an important class of small molecules, have received considerable attention in recent years due to their wide range of biological applications. Various molecular targeted agents with arylurea scaffold as potential enzyme/receptor inhibitors were constructed with the successful development of sorafenib and regorafenib. This review focuses on those arylureas possessing anti-cancer activities from 2010 to date. According to their different mechanisms of action, these arylureas are divided into the following six categories: (1) Ras/Raf/MEK/ERK signaling pathway inhibitors; (2) tumor angiogenesis inhibitors, their targets include vascular endothelial growth factor receptors (VEGFRs), fibroblast growth factor receptors (FGFRs), platelet-derived growth factor receptors (PDGFRs), epidermal growth factor receptors (EGFRs), insulin-like growth factor 1 receptor (IGF-1R), Fms-like tyrosine kinase 3 (FLT3), c-Kit, MET, and Smoothened (Smo); (3) PI3K/AKT/mTOR signaling pathway inhibitors; (4) cell cycle inhibitors, their targets include checkpoint kinases (Chks), cyclin-dependent kinases (CDKs), Aurora, SUMO activating enzyme 1 (SUMO E1), tubulin, and DNA; (5) tumor differentiation, migration, and invasion inhibitors, their targets include matrix metalloproteinases (MMPs), LIM kinase (Limk), nicotinamide phosphoribosyltransferase (Nampt), and histone deacetylase (HDAC); (6) arylureas from the rational modification of natural products...
July 7, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28681592/oleanolic-acid-promotes-neuronal-differentiation-and-histone-deacetylase-5-phosphorylation-in-rat-hippocampal-neurons
#8
Hye-Ryeong Jo, Sung Eun Wang, Yong-Seok Kim, Chang Ho Lee, Hyeon Son
Oleanolic acid (OA) has neurotrophic effects on neurons, although its use as a neurological drug requires further research. In the present study, we investigated the effects of OA and OA derivatives on the neuronal differentiation of rat hippocampal neural progenitor cells. In addition, we investigated whether the class II histone deacetylase (HDAC) 5 mediates the gene expression induced by OA. We found that OA and OA derivatives induced the formation of neurite spines and the expression of synapse-related molecules...
June 30, 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28646552/targeting-histone-deacetylase-4-ubc9-impairs-dna-repair-for-radiosensitization-of-hepatocellular-carcinoma-cells
#9
Chiao-Ling Tsai, Wei-Lin Liu, Feng-Ming Hsu, Po-Sheng Yang, Ruoh-Fang Yen, Kai-Yuan Tzen, Ann-Lii Cheng, Pei-Jer Chen, Jason Chia-Hsien Cheng, Hsien Cheng
Several strategies to improve the efficacy of radiation therapy against hepatocellular carcinoma (HCC) have been investigated. One approach was to develop radiosensitizing compounds. Because histone deacetylase 4 (HDAC4) is highly expressed in liver cancer and known to regulate oncogenesis through chromatin structure remodeling and controlling protein access to DNA, we postulated that HDAC4 inhibition might enhance radiation's effect on HCC cells. HCC cell lines (Huh7 and PLC5) and an ectopic xenograft were pretreated with HDAC inhibitor or shRNA to knock down expression of HDAC4, and then irradiated (2...
June 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28630710/hdac-inhibitor-conjugated-polymeric-prodrug-micelles-for-doxorubicin-delivery
#10
Suchithra A Senevirathne, Katherine E Washington, Jason B Miller, Michael C Biewer, David Oupicky, Daniel J Siegwart, Mihaela C Stefan
Amphiphilic diblock copolymers bearing histone deacetylase inhibitors (HDACi) (4-phenyl butyric acid and valproic acid) were synthesized by the ring-opening polymerization of γ-4-phenylbutyrate-ε-caprolactone (PBACL), γ-valproate-ε-caprolactone (VPACL), and ε-caprolactone (CL) from a poly(ethylene glycol) macroinitiator (PEG). These amphiphilic diblock copolymers self-assembled into stable pro-drug micelles and demonstrated excellent biocompatibility. High loading of doxorubicin (DOX) up to 5.1 wt% was achieved...
March 21, 2017: Journal of Materials Chemistry. B, Materials for Biology and Medicine
https://www.readbyqxmd.com/read/28615712/cell-specific-expression-of-aquaporin-5-aqp5-in-alveolar-epithelium-is-directed-by-gata6-sp1-via-histone-acetylation
#11
Per Flodby, Changgong Li, Yixin Liu, Hongjun Wang, Megan E Rieger, Parviz Minoo, Edward D Crandall, David K Ann, Zea Borok, Beiyun Zhou
Epigenetic regulation of differentiation-related genes is poorly understood. We previously reported that transcription factors GATA6 and Sp1 interact with and activate the rat proximal 358-bp promoter/enhancer (p358P/E) of lung alveolar epithelial type I (AT1) cell-specific gene aquaporin-5 (Aqp5). In this study, we found that histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) increased AQP5 expression and Sp1-mediated transcription of p358P/E. HDAC3 overexpression inhibited Sp1-mediated Aqp5 activation, while HDAC3 knockdown augmented AQP5 protein expression...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28612091/intracellular-vorinostat-accumulation-and-its-relationship-to-histone-deacetylase-activity-in-soft-tissue-sarcoma-patients
#12
Jürgen Burhenne, Lu Liu, Christoph E Heilig, Andreas D Meid, Margarete Leisen, Thomas Schmitt, Bernd Kasper, Walter E Haefeli, Gerd Mikus, Gerlinde Egerer
PURPOSE: In the regulation of chromatin-structure and histone function, histone deacetylases (HDACs) are key enzymes and thus modulators of epigenetic regulation and gene expression. Accesses of the HDAC inhibitor vorinostat to intracellular compartments are essential to exert epigenetic effects. METHODS: In ten sarcoma patients receiving oral Zolinza (400 mg qd) vorinostat concentrations in plasma and peripheral blood mononuclear cells (PBMCs) were quantified using validated LC/MS/MS assays to determine intracellular and extracellular pharmacokinetic data...
June 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28607401/novel-class-iia-selective-histone-deacetylase-inhibitors-discovered-using-an-in-silico-virtual-screening-approach
#13
Kai-Cheng Hsu, Chang-Yi Liu, Tony Eight Lin, Jui-Hua Hsieh, Tzu-Ying Sung, Hui-Ju Tseng, Jinn-Moon Yang, Wei-Jan Huang
Histone deacetylases (HDAC) contain eighteen isoforms that can be divided into four classes. Of these isoform enzymes, class IIa (containing HDAC4, 5, 7 and 9) target unique substrates, some of which are client proteins associated with epigenetic control. Class IIa HDACs are reportedly associated with some neuronal disorders, making HDACs therapeutic targets for treating neurodegenerative diseases. Additionally, some reported HDAC inhibitors contain hydroxamate moiety that chelates with zinc ion to become the cofactor of HDAC enzymes...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592694/opening-a-new-time-window-for-treatment-of-stroke-by-targeting-hdac2
#14
Yu-Hui Lin, Jian Dong, Ying Tang, Huan-Yu Ni, Yu Zhang, Ping Su, Hai-Ying Liang, Meng-Cheng Yao, Hong-Jin Yuan, Dong-Liang Wang, Lei Chang, Hai-Yin Wu, Chun-Xia Luo, Dong-Ya Zhu
Narrow therapeutic window limits treatments with thrombolysis and neuroprotection for most stroke patients. Widening therapeutic window remains a critical challenge. Understanding the key mechanisms underlying the pathophysiological events in the peri-infarct area where secondary injury coexists with neuroplasticity over days to weeks may offer an opportunity for expanding the therapeutic window. Here we show that ischemia-induced HDAC2 up-regulation from 5 to 7 days after stroke plays a crucial role. In this window phase, suppressing HDAC2 in the peri-infarct cortex of rodents by HDAC inhibitors, knockdown or knockout of HDAC2 promoted recovery of motor function from stroke via epigenetically enhancing cells survival and neuroplasticity of surviving neurons as well as reducing neuroinflammation, whereas over-expressing HDAC2 worsened stroke-induced functional impairment of both WT and HDAC2 CKO mice...
June 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28567090/expression-of-class-i-and-class-ii-a-b-histone-deacetylase-is-dysregulated-in-hypertensive-animal-models
#15
Hae Jin Kee, Gwi Ran Kim, Ming Quan Lin, Sin Young Choi, Yuhee Ryu, Li Jin, Zhe Hao Piao, Myung Ho Jeong
BACKGROUND AND OBJECTIVES: Dysregulation of histone deacetylase expression and enzymatic activity is associated with a number of diseases. It has been reported that protein levels of histone deacetylase (HDAC)1 and HDAC5 increase during human pulmonary hypertension, and that the enzymatic activity of HDAC6 is induced in a chronic hypertensive animal model. This study investigated the protein expression profiles of class I and II a/b HDACs in three systemic hypertension models. SUBJECTS AND METHODS: We used three different hypertensive animal models: (i) Wistar-Kyoto rats (n=8) and spontaneously hypertensive rats (SHR; n=8), (ii) mice infused with saline or angiotensin II to induce hypertension, via osmotic mini-pump for 2 weeks, and (iii) mice that were allowed to drink L-N(G)-nitro-L-arginine methyl ester (L-NAME) to induce hypertension...
May 2017: Korean Circulation Journal
https://www.readbyqxmd.com/read/28560069/the-identification-and-validation-of-trichosstatin-a-as-a-potential-inhibitor-of-colon-tumorigenesis-and-colon-cancer-stem-like-cells
#16
Tse-Hung Huang, Szu-Yuan Wu, Yan-Jiun Huang, Po-Li Wei, Alexander Th Wu, Tsu-Yi Chao
Colon cancer is one of the most prevalent cancer types in developed countries. Metastasis and drug resistance are two contributing factors to the high mortality rate. Accumulating evidence suggest that cancer stem-like cells (CSCs) represents as a major contributor to these malignant features. Here, we identified and isolated colon cancer stem-like cells using side-population (SP) method from human colon cancer cell lines. SP colon cells demonstrate cancer stem-like cell properties including enhanced sphere-forming ability and resistance towards fluorouracil (5-FU)...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28554803/integrated-omics-approaches-to-characterize-a-nuclear-receptor-corepressor-associated-histone-deacetylase-in-mouse-skeletal-muscle
#17
REVIEW
Yingyun Gong, Rui Cao, Guolian Ding, Sungguan Hong, Wenjun Zhou, Wenyun Lu, Manashree Damle, Bin Fang, Chuhan C Wang, Justin Qian, Natasha Lie, Cristina Lanzillotta, Joshua D Rabinowitz, Zheng Sun
Nuclear receptors regulate gene expression by differentially binding to coactivators or corepressors in a ligand-dependent manner, which further recruits a set of epigenome-modifying enzymes that remodel chromatin conformation. Histone acetylation is a major epigenomic change controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDAC3 is the only HDAC that confers the enzymatic activity to the complexes nucleated by nuclear receptor corepressors NCoR and SMRT. To address the metabolic function of HDAC3, we have deleted it specifically in mouse skeletal muscles...
May 26, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28548643/condensed-versus-standard-schedule-of-high-dose-cytarabine-consolidation-therapy-with-pegfilgrastim-growth-factor-support-in-acute-myeloid-leukemia
#18
S Jaramillo, A Benner, J Krauter, H Martin, T Kindler, M Bentz, H R Salih, G Held, C-H Köhne, K Götze, M Lübbert, A Kündgen, P Brossart, M Wattad, H Salwender, B Hertenstein, D Nachbaur, G Wulf, H-A Horst, H Kirchen, W Fiedler, A Raghavachar, G Russ, S Kremers, E Koller, V Runde, G Heil, D Weber, G Göhring, K Döhner, A Ganser, H Döhner, R F Schlenk
The aim of this cohort study was to compare a condensed schedule of consolidation therapy with high-dose cytarabine on days 1, 2 and 3 (HDAC-123) with the HDAC schedule given on days 1, 3 and 5 (HDAC-135) as well as to evaluate the prophylactic use of pegfilgrastim after chemotherapy in younger patients with acute myeloid leukemia in first complete remission. One hundred and seventy-six patients were treated with HDAC-135 and 392 patients with HDAC-123 with prophylactic pegfilgrastim at days 10 and 8, respectively, in the AMLSG 07-04 and the German AML Intergroup protocol...
May 26, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28533215/inhibition-of-hdac3-prevents-diabetic-cardiomyopathy-in-ove26-mice-via-epigenetic-regulation-of-dusp5-erk1-2-pathway
#19
Zheng Xu, Qian Tong, Zhiguo Zhang, Shudong Wang, Yang Zheng, Qiuju Liu, Lingbo Qian, Shao-Yu Chen, Jian Sun, Lu Cai
Inhibition of total histone deacetylases (HDACs) was phenomenally associated with the prevention of diabetic cardiomyopathy (DCM). However, which specific HDAC plays the key role in DCM remains unclear. The present study was designed to determine whether DCM can be prevented by specific inhibition of HDAC3 and to elucidate the mechanisms by which inhibition of HDAC3 prevent DCM. Type 1 diabetes OVE26 and age-matched wild-type mice were given the selective HDAC3 inhibitor RGFP966 or vehicle for 3 months. These mice were then sacrificed immediately or 3 months later for cardiac function and pathological examination...
May 22, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28524836/effect-of-histone-deacetylase-inhibition-on-the-expression-of-multidrug-resistance-associated-protein-2-in-a-human-placental-trophoblast-cell-line
#20
Hong-Yu Duan, Dan Ma, Kai-Yu Zhou, Tao Wang, Yi Zhang, Yi-Fei Li, Jin-Lin Wu, Yi-Min Hua, Chuan Wang
BACKGROUND: Placental multidrug resistance-associated protein 2 (MRP2), encoded by ABCC2 gene in human, plays a significant role in regulating drugs' transplacental transfer rates. Studies on placental MRP2 regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. Currently, the roles of epigenetic mechanisms in regulating placental drug transporters are still unclear. This study aimed to investigate the effect of histone deacetylases (HDACs) inhibition on MRP2 expression in the placental trophoblast cell line and to explore whether HDAC1/2/3 are preliminarily involved in this process...
June 5, 2017: Chinese Medical Journal
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