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histone deacetylase metabolic

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https://www.readbyqxmd.com/read/28447074/chidamide-tablets-hdac-inhibition-to-treat-lymphoma
#1
Y Xu, P Zhang, Y Liu
Chidamide is the first oral subtype-selective histone deacetylase inhibitor (HDACI) approved in China as well as the first HDACI of the benzamide class approved for the treatment of relapsed and refractory peripheral T-cell lymphoma (PTCL). This review addresses detailed information regarding chidamide, including the mechanism of action, preclinical pharmacology, pharmacokinetics and metabolism, clinical studies and application, safety, drug interactions and ongoing clinical trials. Although twice-weekly chidamide monotherapy has been recommended based on the evidence from preclinical and clinical studies with tolerable toxicities, its clinical efficacy could be further increased by combination with multidrug chemotherapy or chemo-free regimens...
March 2017: Drugs of Today
https://www.readbyqxmd.com/read/28446321/-drug-resistant-mechanism-of-multiple-myeloma-and-its-therapy-combined-with-hdaci-review
#2
Liu-Fang Gu, Xiao-Guang Cui, Xing-Mei Cao, She-Ping Chen
Drug resistance of multiple myeloma(MM) has become more and more common, and greatly decreased the survival rate of these patients. The occurence of drug-resistance involves in many factors such as bone marrow microenveronment, tumor cell self-metabolism, cytokines, specific targets and so on. In this review, the potential mechanisms of resistance to glucocorticoid/proteasome inhibitor/immunomodulatory druges are briefly expounded in the aspect of tumor cell self-metabolism, including the changes of heat slock protein expression, mRNA expression, related cytokine levels and down-regulation of thalidomid-effecting site CRBN expression...
April 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28444216/dietary-metabolites-derived-from-gut-microbiota-critical-modulators-of-epigenetic-changes-in-mammals
#3
Mohd Iqbal Bhat, Rajeev Kapila
The mammalian gastrointestinal tract harbors trillions of commensal microorganisms, collectively known as the microbiota. The microbiota is a critical source of environmental stimuli and, thus, has a tremendous impact on the health of the host. The microbes within the microbiota regulate homeostasis within the gut, and any alteration in their composition can lead to disorders that include inflammatory bowel disease, allergy, autoimmune disease, diabetes, mental disorders, and cancer. Hence, restoration of the gut flora following changes or imbalance is imperative for the host...
April 22, 2017: Nutrition Reviews
https://www.readbyqxmd.com/read/28439316/epigenetic-assays-for-chemical-biology-and-drug-discovery
#4
REVIEW
Sheraz Gul
The implication of epigenetic abnormalities in many diseases and the approval of a number of compounds that modulate specific epigenetic targets in a therapeutically relevant manner in cancer specifically confirms that some of these targets are druggable by small molecules. Furthermore, a number of compounds are currently in clinical trials for other diseases including cardiovascular, neurological and metabolic disorders. Despite these advances, the approved treatments for cancer only extend progression-free survival for a relatively short time and being associated with significant side effects...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28437180/a-novel-drug-induced-hybrid-electrospun-pcl-cell-derived-ecm-scaffold-for-liver-tissue-engineering
#5
Rhiannon Grant, David Hay, Anthony Callanan
Liver transplant is the only treatment option for patients with end-stage liver failure, however there are too few donor livers available for transplant. Whole organ tissue engineering presents a potential solution to the problem of rapidly escalating donor liver shortages world-wide. A major challenge for liver tissue engineers is the creation of a hepatocyte micro-environment; a niche in which liver cells can survive and function optimally. While polymers and decellularized tissues pose an attractive option for scaffold manufacturing, neither alone has thus far proved sufficient...
February 24, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28414307/metabolic-inhibitors-accentuate-the-anti-tumoral-effect-of-hdac5-inhibition
#6
E Hendrick, P Peixoto, A Blomme, C Polese, N Matheus, J Cimino, A Frère, A Mouithys-Mickalad, D Serteyn, L Bettendorff, B Elmoualij, P De Tullio, G Eppe, F Dequiedt, V Castronovo, D Mottet
The US FDA approval of broad-spectrum histone deacetylase (HDAC) inhibitors has firmly laid the cancer community to explore HDAC inhibition as a therapeutic approach for cancer treatment. Hitting one HDAC member could yield clinical benefit but this required a complete understanding of the functions of the different HDAC members. Here we explored the consequences of specific HDAC5 inhibition in cancer cells. We demonstrated that HDAC5 inhibition induces an iron-dependent reactive oxygen species (ROS) production, ultimately leading to apoptotic cell death as well as mechanisms of mitochondria quality control (mitophagy and mitobiogenesis)...
April 17, 2017: Oncogene
https://www.readbyqxmd.com/read/28404582/histone-deacetylase-activity-modulates-exercise-induced-skeletal-muscle-plasticity-in-zebrafish-danio-rerio
#7
Alec Izaac Marcus Simmonds, Frank Seebacher
Aerobic exercise has a positive impact on animals by enhancing skeletal muscle function and locomotor performance. Responses of skeletal muscle to exercise involve changes in energy metabolism, calcium handling, and the composition of contractile protein isoforms, which together influence contractile properties. Histone deacetylases (HDAC) can cause short-term changes in gene expression, and may thereby mediate plasticity in contractile properties of skeletal muscle in response to exercise. The aim of this project was to determine (in zebrafish, Danio rerio) the traits that mediate inter-individual differences in sustained and sprint performance, and to determine whether inhibiting class I and II HDACs mediates exercise-induced changes in these traits...
April 12, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28375564/effects-of-histone-deacetylase-inhibitors-on-regenerative-cell-responses-in-human-dental-pulp-cells
#8
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/28373363/re-engineering-the-pancreas-tumor-microenvironment-a-regenerative-program-hacked
#9
EDITORIAL
Gerard I Evan, Nasun Hah, Trevor D Littlewood, Nicole M Sodir, Tania Campos, Michael Downes, Ronald M Evans
The "hallmarks" of pancreatic ductal adenocarcinoma (PDAC) include proliferative, invasive, and metastatic tumor cells and an associated dense desmoplasia comprised of fibroblasts, pancreatic stellate cells, extracellular matrix, and immune cells. The oncogenically activated pancreatic epithelium and its associated stroma are obligatorily interdependent, with the resulting inflammatory and immunosuppressive microenvironment contributing greatly to the evolution and maintenance of PDAC. The peculiar pancreas-specific tumor phenotype is a consequence of oncogenes hacking the resident pancreas regenerative program, a tissue-specific repair mechanism regulated by discrete super enhancer networks...
April 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28371201/ketone-bodies-mimic-the-life-span-extending-properties-of-caloric-restriction
#10
REVIEW
Richard L Veech, Patrick C Bradshaw, Kieran Clarke, William Curtis, Robert Pawlosky, M Todd King
The extension of life span by caloric restriction has been studied across species from yeast and Caenorhabditis elegans to primates. No generally accepted theory has been proposed to explain these observations. Here, we propose that the life span extension produced by caloric restriction can be duplicated by the metabolic changes induced by ketosis. From nematodes to mice, extension of life span results from decreased signaling through the insulin/insulin-like growth factor receptor signaling (IIS) pathway...
April 3, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28364192/protein-arginine-methylation-a-prominent-modification-and-its-demethylation
#11
REVIEW
Juste Wesche, Sarah Kühn, Benedikt M Kessler, Maayan Salton, Alexander Wolf
Arginine methylation of histones is one mechanism of epigenetic regulation in eukaryotic cells. Methylarginines can also be found in non-histone proteins involved in various different processes in a cell. An enzyme family of nine protein arginine methyltransferases catalyses the addition of methyl groups on arginines of histone and non-histone proteins, resulting in either mono- or dimethylated-arginine residues. The reversibility of histone modifications is an essential feature of epigenetic regulation to respond to changes in environmental factors, signalling events, or metabolic alterations...
March 31, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28350877/exposure-to-atheroma-relevant-7-oxysterols-causes-proteomic-alterations-in-cell-death-cellular-longevity-and-lipid-metabolism-in-thp-1-macrophages
#12
Liam J Ward, Stefan A Ljunggren, Helen Karlsson, Wei Li, Xi-Ming Yuan
The 7-oxysterols are recognised as strong enhancers of inflammatory processes in foamy macrophages. Atheroma-relevant 7-oxysterol mixtures induce a mixed type of cell death in macrophages, and trigger cellular oxidative stress responses, which mimic oxidative exposures observed in atherosclerotic lesions. However, the macrophage proteome has not previously been determined in the 7-oxysterol treated cell model. The aim of the present study was to determine the specific effects of an atheroma-relevant 7-oxysterol mixture on human macrophage proteome...
2017: PloS One
https://www.readbyqxmd.com/read/28322796/modulation-of-the-sphingolipid-rheostat-is-involved-in-paclitaxel-resistance-of-the-human-prostate-cancer-cell-line-pc3-pr
#13
Yuka Aoyama, Sayaka Sobue, Naoki Mizutani, Chisato Inoue, Yoshiyuki Kawamoto, Yuji Nishizawa, Masatoshi Ichihara, Mamoru Kyogashima, Motoshi Suzuki, Yoshinoti Nozawa, Takashi Murate
Taxoids are anti-cancer drugs frequently used to treat solid tumors, but they are sometimes ineffective and tumors may become resistant to their action. Here, we examined the involvement of sphingolipid metabolic enzymes in paclitaxel (PTX) resistance using a human prostate cancer cell line, PC3, and its PTX-resistant subline, PC3-PR. PTX (20 nM) suppressed cell proliferation and increased various ceramide species in PC3, but not PC3-PR, cells. PC3-PR contained higher S1P levels than did PC3, regardless of PTX treatment...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28315153/effects-of-histone-deacetylase-inhibitory-prodrugs-on-epigenetic-changes-and-dna-damage-response-in-tumor-and-heart-of-glioblastoma-xenograft
#14
Nataly Tarasenko, Abraham Nudelman, Gabriela Rozic, Suzanne M Cutts, Ada Rephaeli
The histone deacetylase (HDAC) inhibitory prodrugs of butyric (AN7) and valproic (AN446) acids, which release the active acids upon metabolic degradation, were studied examining their differential effects on the viability, HDAC inhibitory activity and the DNA damage response (DDR), in glioblastoma cell and normal human astrocytes (NHAs). In xenografts of glioblastoma, AN7 or AN446 given or the combination of each of them with Dox augmented the anticancer activity of Dox and protected the heart from its toxicity...
March 17, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28287402/hdac6-mediated-acetylation-of-lipid-droplet-binding-protein-cidec-regulates-fat-induced-lipid-storage
#15
Hui Qian, Yuanying Chen, Zongqian Nian, Lu Su, Haoyong Yu, Feng-Jung Chen, Xiuqin Zhang, Wenyi Xu, Linkang Zhou, Jiaming Liu, Jinhai Yu, Luxin Yu, Yan Gao, Hongchao Zhang, Haihong Zhang, Shimin Zhao, Li Yu, Rui-Ping Xiao, Yuqian Bao, Shaocong Hou, Pingping Li, Jiada Li, Haiteng Deng, Weiping Jia, Peng Li
Obesity is characterized by aberrant fat accumulation. However, the intracellular signaling pathway that senses dietary fat and leads to fat storage remains elusive. Here, we have observed that the levels of histone deacetylase 6 (HDAC6) and the related family member HDAC10 are markedly reduced in adipose tissues of obese animals and humans. Mice with adipocyte-specific depletion of Hdac6 exhibited increased fat accumulation and reduced insulin sensitivity. In normal adipocytes, we found that reversal of P300/CBP-associated factor-induced (PCAF-induced) acetylation at K56 on cell death-inducing DFFA-like effector C (CIDEC, also known as FSP27) critically regulated lipid droplet fusion and lipid storage...
April 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28262837/inhibiting-histone-deacetylases-suppresses-glucose-metabolism-and-hepatocellular-carcinoma-growth-by-restoring-fbp1-expression
#16
Jing Yang, Xin Jin, Yuqian Yan, Yingjie Shao, Yunqian Pan, Lewis R Roberts, Jun Zhang, Haojie Huang, Jingting Jiang
Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers in the world. Elevated glucose metabolism in the availability of oxygen, a phenomenon called the Warburg effect, is important for cancer cell growth. Fructose-1,6-bisphosphatase (FBP1) is a rate-limiting enzyme in gluconeogenesis and is frequently lost in various types of cancer. Here, we demonstrated that expression of FBP1 was downregulated in HCC patient specimens and decreased expression of FBP1 associated with poor prognosis. Low expression of FBP1 correlated with high levels of histone deacetylase 1 (HDAC1) and HDAC2 proteins in HCC patient tissues...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28261475/the-action-of-%C3%AE-hydroxybutyrate-on-the-growth-metabolism-and-global-histone-h3-acetylation-of-spontaneous-mouse-mammary-tumours-evidence-of-a-%C3%AE-hydroxybutyrate-paradox
#17
Loreta M Rodrigues, Santiago Uribe-Lewis, Basetti Madhu, Davina J Honess, Marion Stubbs, John R Griffiths
BACKGROUND: Ketone bodies have both metabolic and epigenetic roles in cancer. In several studies, they showed an anti-cancer effect via inhibition of histone deacetylases; however, other studies observed faster tumour growth. The related molecule butyrate also inhibits growth of some cancer cells and accelerates it in others. This "butyrate paradox" is thought to be due to butyrate mediating histone acetylation and thus inhibiting cell proliferation in cancers that preferentially utilise glucose (the Warburg effect); whereas in cells that oxidise butyrate as a fuel, it fails to reach inhibitory concentrations and can stimulate growth...
2017: Cancer & Metabolism
https://www.readbyqxmd.com/read/28240298/glucocorticoid-receptor-positively-regulates-transcription-of-fndc5-in-the-liver
#18
Hyoung Kyu Kim, Yu Jeong Jeong, In-Sung Song, Yeon Hee Noh, Kyo Won Seo, Min Kim, Jin Han
Irisin is secreted by skeletal muscle during exercise and influences energy and metabolic homeostasis. This hormone is a cleaved and secreted fragment of fibronectin type III domain-containing 5 (FNDC5). Elucidation of the FNDC5 gene regulation mechanism is necessary to clarify the function of irisin as a potential therapeutic target in human metabolic diseases. Thus, we investigated the genetic and epigenetic mechanisms that regulate expression of the FNDC5 gene. FNDC5 mRNA was strong expressed in major energy-dependent human tissues, including heart, brain, liver, and skeletal muscle...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28228253/sirt6-suppresses-cancer-stem-like-capacity-in-tumors-with-pi3k-activation-independently-of-its-deacetylase-activity
#19
Rafael M Ioris, Mirco Galié, Giorgio Ramadori, Jason G Anderson, Anne Charollais, Georgia Konstantinidou, Xavier Brenachot, Ebru Aras, Algera Goga, Nicholas Ceglia, Carlos Sebastián, Denis Martinvalet, Raul Mostoslavsky, Pierre Baldi, Roberto Coppari
Cancer stem cells (CSCs) have high tumorigenic capacity. Here, we show that stem-like traits of specific human cancer cells are reduced by overexpression of the histone deacetylase sirtuin 6 (SIRT6). SIRT6-sensitive cancer cells bear mutations that activate phosphatidylinositol-3-kinase (PI3K) signaling, and overexpression of SIRT6 reduces growth, progression, and grade of breast cancer in a mouse model with PI3K activation. Tumor metabolomic and transcriptomic analyses reveal that SIRT6 overexpression dampens PI3K signaling and stem-like characteristics and causes metabolic rearrangements in this cancer model...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28219521/butyrate-influences-intracellular-levels-of-adenine-and-adenine-derivatives-in-the-fungus-penicillium-restrictum
#20
Christoph Zutz, Yi Ming Chiang, Bettina Faehnrich, Markus Bacher, Roland Hellinger, Bernhard Kluger, Martin Wagner, Joseph Strauss, Kathrin Rychli
Butyrate, a small fatty acid, has an important role in the colon of ruminants and mammalians including the inhibition of inflammation and the regulation of cell proliferation. There is also growing evidence that butyrate is influencing the histone structure in mammalian cells by inhibition of histone deacetylation. Butyrate shows furthermore an antimicrobial activity against fungi, yeast and bacteria, which is linked to its toxicity at a high concentration. In fungi there are indications that butyrate induces the production of secondary metabolites potentially via inhibition of histone deacetylases...
April 2017: Microbiological Research
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