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histone deacetylase reactive oxygen

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https://www.readbyqxmd.com/read/29789603/vorinostat-and-quinacrine-have-synergistic-effects-in-t-cell-acute-lymphoblastic-leukemia-through-reactive-oxygen-species-increase-and-mitophagy-inhibition
#1
Bo Jing, Jin Jin, Rufang Xiang, Meng Liu, Li Yang, Yin Tong, Xinhua Xiao, Hu Lei, Wei Liu, Hanzhang Xu, Jiong Deng, Li Zhou, Yingli Wu
Despite recent progress in the treatment, the outcome of adult acute T-cell lymphoblastic leukemia (T-ALL) is poor. Development of novel approach to combat this disease is urgently required. Vorinostat, a pan-histone deacetylase (HDAC) inhibitor, exerts promising anticancer activity in a variety of solid and hematologic malignancies. However, the efficacy of vorinostat monotherapy is unsatisfactory. Here, we show that quinacrine (QC), an anti-malaria drug with potent autophagy inhibitory activity, could synergistically enhance vorinostat-induced cell death at a non-toxic concentration...
May 22, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29754815/an-acquired-vulnerability-of-drug-resistant-melanoma-with-therapeutic-potential
#2
Liqin Wang, Rodrigo Leite de Oliveira, Sanne Huijberts, Evert Bosdriesz, Nora Pencheva, Diede Brunen, Astrid Bosma, Ji-Ying Song, John Zevenhoven, G Tjitske Los-de Vries, Hugo Horlings, Bastiaan Nuijen, Jos H Beijnen, Jan H M Schellens, Rene Bernards
BRAF(V600E) mutant melanomas treated with inhibitors of the BRAF and MEK kinases almost invariably develop resistance that is frequently caused by reactivation of the mitogen activated protein kinase (MAPK) pathway. To identify novel treatment options for such patients, we searched for acquired vulnerabilities of MAPK inhibitor-resistant melanomas. We find that resistance to BRAF+MEK inhibitors is associated with increased levels of reactive oxygen species (ROS). Subsequent treatment with the histone deacetylase inhibitor vorinostat suppresses SLC7A11, leading to a lethal increase in the already-elevated levels of ROS in drug-resistant cells...
April 28, 2018: Cell
https://www.readbyqxmd.com/read/29710809/anti-oxidant-and-anti-inflammatory-activity-of-ketogenic-diet-new-perspectives-for-neuroprotection-in-alzheimer-s-disease
#3
REVIEW
Alessandro Pinto, Alessio Bonucci, Elisa Maggi, Mariangela Corsi, Rita Businaro
The ketogenic diet, originally developed for the treatment of epilepsy in non-responder children, is spreading to be used in the treatment of many diseases, including Alzheimer’s disease. The main activity of the ketogenic diet has been related to improved mitochondrial function and decreased oxidative stress. B-Hydroxybutyrate, the most studied ketone body, has been shown to reduce the production of reactive oxygen species (ROS), improving mitochondrial respiration: it stimulates the cellular endogenous antioxidant system with the activation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2), it modulates the ratio between the oxidized and reduced forms of nicotinamide adenine dinucleotide (NAD⁺/NADH) and it increases the efficiency of electron transport chain through the expression of uncoupling proteins...
April 28, 2018: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/29704392/the-nephroprotective-effect-of-ms-275-on-lipopolysaccharide-lps-induced-acute-kidney-injury-by-inhibiting-reactive-oxygen-species-ros-oxidative-stress-and-endoplasmic-reticulum-stress
#4
Haiyue Zhang, Wenbin Zhang, Fangzhou Jiao, Xun Li, Hong Zhang, Luwen Wang, Zuojiong Gong
BACKGROUND Histone deacetylase (HDAC) inhibitors can attenuate acute kidney injury (AKI)-mediated damage and reduce fibrosis in kidney disease models. The aim of the present study was to investigate the effects of the HDAC inhibitor MS-275 on lipopolysaccharide (LPS)-induced AKI and the associated mechanisms. MATERIAL AND METHODS A LPS-induced model in 6-8 weeks-old mice was established by intraperitoneal injection of LPS (10 mg/kg), with pre-treatment of MS-275 (2 mg/kg/day) administered intraperitoneally for five days...
April 28, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29655790/hdac11-deletion-reduces-fructose-induced-cardiac-dyslipidemia-apoptosis-and-inflammation-by-attenuating-oxidative-stress-injury
#5
Xiao-Di Fan, Lan-Lan Wan, Man Duan, Shan Lu
Diabetes mellitus (DM) is a risk factor for abnormal heart development, but the molecular mechanism remains obscure. Histone deacetylase 11 (HDAC11), the most recently identified histone deacetylase, is the sole member of class IV HDACs. However, its role in diabetic cardiac injury is still poorly understood. In the present study, we attempted to explore the effects of HDAC11 on fructose (Fru)-induced cardiac injury using the wild type (HDAC11+/+ ) and knockout (HDAC11-/- ) mice. The results indicated that HDAC11 was significantly expressed in human and mouse diabetic heart failure (DHF) hearts...
April 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29587244/epigenetic-regulation-of-vascular-nadph-oxidase-expression-and-reactive-oxygen-species-production-by-histone-deacetylase-dependent-mechanisms-in-experimental-diabetes
#6
Simona-Adriana Manea, Mihaela-Loredana Antonescu, Ioana Madalina Fenyo, Monica Raicu, Maya Simionescu, Adrian Manea
Reactive oxygen species (ROS) generated by up-regulated NADPH oxidase (Nox) contribute to structural-functional alterations of the vascular wall in diabetes. Epigenetic mechanisms, such as histone acetylation, emerged as important regulators of gene expression in cardiovascular disorders. Since their role in diabetes is still elusive we hypothesized that histone deacetylase (HDAC)-dependent mechanisms could mediate vascular Nox overexpression in diabetic conditions. Non-diabetic and streptozotocin-induced diabetic C57BL/6J mice were randomized to receive vehicle or suberoylanilide hydroxamic acid (SAHA), a pan-HDAC inhibitor...
March 17, 2018: Redox Biology
https://www.readbyqxmd.com/read/29453918/high-dose-of-histone-deacetylase-inhibitors-affects-insulin-secretory-mechanism-of-pancreatic-beta-cell-line
#7
Eiji Yamato
OBJECTIVE: Histone deacytylase inhibitors (HDACis) inhibit the deacetylation of the lysine residue of proteins, including histones, and regulate the transcription of a variety of genes. Recently, HDACis have been used clinically as anti-cancer drugs and possible anti-diabetic drugs. Even though HDACis have been proven to protect the cytokine-induced damage of pancreatic beta cells, evidence also shows that high doses of HDACis are cytotoxic. In the present study, we, therefore, investigated the eff ect of HDACis on insulin secretion in a pancreatic beta cell line...
January 1, 2018: Endocrine Regulations
https://www.readbyqxmd.com/read/29445146/dural-effects-of-oxidative-stress-on-cardiomyogenesis-via-gata4-transcription-and-protein-ubiquitination
#8
Tao Li, Xia Zhang, Kesheng Jiang, Jing Liu, Zhiqiang Liu
Oxidative stress generates reactive oxygen species (ROS) that can promote or inhibit cardiac differentiation of stem cells dependent on the intensity of stimuli as well as cellular context in redox and differentiation status. In the current study, we confirmed that suitable intensity of hydrogen peroxide at the formation stage of embryoid bodies (EBs) effectively favored the formation of spontaneously beating cardiomyocytes from P19 embryonal carcinoma cells. Mechanistic studies implicated that extrinsic ROS enhanced the Caspase-mediated degradation of Oct4 and Nanog, two factors that governing pluripotent property...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29423093/combination-of-a-hypomethylating-agent-and-inhibitors-of-parp-and-hdac-traps-parp1-and-dnmt1-to-chromatin-acetylates-dna-repair-proteins-down-regulates-nurd-and-induces-apoptosis-in-human-leukemia-and-lymphoma-cells
#9
Benigno C Valdez, Yang Li, David Murray, Yan Liu, Yago Nieto, Richard E Champlin, Borje S Andersson
Combination of drugs that target different aspects of aberrant cellular processes is an efficacious treatment for hematological malignancies. Hypomethylating agents (HMAs) and inhibitors of poly(ADP-ribose) polymerases (PARPis) and histone deacetylases (HDACis) are clinically active anti-tumor drugs. We hypothesized that their combination would be synergistically cytotoxic to leukemia and lymphoma cells. Exposure of AML and lymphoma cell lines to the combination of the PARPi niraparib (Npb), the HMA decitabine (DAC) and the HDACi romidepsin (Rom) or panobinostat (Pano) synergistically inhibited cell proliferation by up to 70% via activation of the ATM pathway, increased production of reactive oxygen species, decreased mitochondrial membrane potential, and activated apoptosis...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29414656/inhibition-of-histone-deacetylase-reduces-lipopolysaccharide-induced-inflammation-in-primary-mammary-epithelial-cells-by-regulating-ros-nf-%C3%B0%C2%BAb-signaling-pathways
#10
Jingjing Wang, Lilei Zhao, Zhengkai Wei, Xu Zhang, Yanan Wang, Fan Li, Yunhe Fu, Bin Liu
Histone deacetylase 6 (HDAC6) is the sole member of the HDAC family, that is predominantly located in the cytoplasm and has substrate specificity for nonhistone proteins, such as α-Tubulin. Although an increasing number of studies have shown that HDAC6 is involved in inflammatory diseases, but little is known about the participation of HDAC6 in the transcriptional regulation of inflammatory cytokines. Here, we examined the effects of Tubastatin (Tub), a highly selective HDAC6 inhibitor, on lipopolysaccharide (LPS)-stimulated primary bovine mammary epithelial cells (bMECs)...
March 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29376873/lentivirus-mediated-hdac3-inhibition-attenuates-oxidative-stress-in-appswe-ps1de9-mice
#11
Linjie Yu, Yi Liu, Yuexinzi Jin, Xiang Cao, Jian Chen, Jiali Jin, Yue Gu, Xinyu Bao, Zhuoying Ren, Yun Xu, Xiaolei Zhu
Amyloid-β (Aβ) induces a burst of oxidative stress and plays a critical role in the pathogenesis of Alzheimer's disease (AD). Our previous results have shown that histone deacetylase 3 (HDAC3) inhibition ameliorates spatial memory deficits and decreases the Aβ burden in the brains of 9-month-old APPswe/PS1dE9 (APP/PS1) mice. In this study, we investigated the role of HDAC3 inhibition in oxidative stress in vivo and in vitro models of AD. HDAC3 was detected mainly in the neurons, and HDAC3 inhibition significantly decreased reactive oxygen species generation and improved primary cortical neuron viability...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29260509/synergistic-anticancer-effect-of-panobinostat-and-topoisomerase-inhibitors-through-ros-generation-and-intrinsic-apoptotic-pathway-induction-in-cervical-cancer-cells
#12
Lubna Wasim, Madhu Chopra
PURPOSE: Various combinations of drugs may be effective in the treatment of different types of cancer. Previously, we have shown that combinations of the histone deacetylase inhibitor panobinostat and the topoisomerase inhibitors topotecan or etoposide act synergistically, but the underlying mode of action has remained unknown. Here, we aimed at uncovering the mechanisms underlying this synergism. METHODS: The effects of (combinations of) panobinostat and topotecan or etoposide on cervical cancer-derived HeLa and SiHa cells were assessed using morphological evaluations, scratch wound healing assays, cell cycle analyses, AO/EB staining assays, Annexin V/PI staining assays, reactive oxygen species (ROS) and mitochondrial membrane potential measurements and Western blotting...
April 2018: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29215703/design-synthesis-and-characterization-of-%C3%AE-%C3%AE-unsaturated-carboxylic-acid-and-its-urea-based-derivatives-that-explores-novel-epigenetic-modulators-in-human-non-small-cell-lung-cancer-a549-cell-line
#13
Anusha Chidambaram, Kavya Sundararaju, Ramesh K Chidambaram, Rajasekaran Subbiah, John M Jayaraj, Karthikeyan Muthusamy, Ravikumar Vilwanathan
Histone deacetylase inhibitors (HDACi) are a small molecule chemotherapeutics that target the chromatin remodeling through the regulation of histone and non-histone proteins. These inhibitors directed against histone deacetylase (HDAC) enzymes have become an important therapeutic tool in oncology; consequently, scientific efforts have fortified the quest for newer and novel HDACi, which forces the design of structurally innovative HDACi. Various urea containing compounds exhibited admirable anticancer activity...
December 7, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29212263/combination-of-betulinic-acid-and-chidamide-inhibits-acute-myeloid-leukemia-by-suppression-of-the-hif1%C3%AE-pathway-and-generation-of-reactive-oxygen-species
#14
Hongyu Zhang, Ling Li, Min Li, Xiaodong Huang, Weiguo Xie, Wei Xiang, Paul Yao
Acute myeloid leukemia (AML) is a heterogeneous disorder of the hematopoietic system with no common genetic "Achilles heel" that can be targeted. Most patients respond well to standard therapy, while a majority relapse, and development of an effective therapy for AML patients is still urgently needed. In this study, we demonstrated that betulinic acid (BA) significantly increased Aryl hydrocarbon receptor (AHR) expression through demethylation on the AHR promoter in AML cells, and the increased AHR expression interacts with and sequesters ARNT, subsequently suppressing hypoxia-inducible factor-1α (HIF1α) pathway...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29190639/induction-of-colon-and-cervical-cancer-cell-death-by-cinnamic-acid-derivatives-is-mediated-through-the-inhibition-of-histone-deacetylases-hdac
#15
Preethi G Anantharaju, Deepa B Reddy, Mahesh A Padukudru, Ch M Kumari Chitturi, Manjunath G Vimalambike, SubbaRao V Madhunapantula
Recent studies from our group and many others have shown the ability of histone deacetylase (HDAC) inhibitors for retarding the growth of carcinomas of cervix, colon and rectum in vitro. A search for naturally occurring HDAC inhibitors continues due to the adverse effects associated with known HDAC inhibitors like SAHA and TSA. Therefore in the current study, naturally occurring cinnamic acids derivatives were screened for HDAC inhibitory effect using in silico docking method which identified cinnamic acids as potential candidates...
2017: PloS One
https://www.readbyqxmd.com/read/29159826/pharmacological-and-molecular-approaches-for-the-treatment-of-%C3%AE-hemoglobin-disorders
#16
REVIEW
Neelam Lohani, Nupur Bhargava, Anjana Munshi, Sivaprakash Ramalingam
β-hemoglobin disorders, such as β-thalassemia and sickle cell anemia are among the most prevalent inherited genetic disorders worldwide. These disorders are caused by mutations in the gene encoding hemoglobin-β (HBB), a vital protein found in red blood cells (RBCs) that carries oxygen from lungs to all parts of the human body. As a consequence, there has been an enduring interest in this field in formulating therapeutic strategies for the treatment of these diseases. Currently, there is no cure available for hemoglobin disorders, although, some patients have been treated with bone marrow transplantation, whose scope is limited because of the difficulty in finding a histocompatible donor and also due to transplant-associated clinical complications that can arise during the treatment...
June 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29130578/sirt3-deregulation-is-linked-to-mitochondrial-dysfunction-in-alzheimer-s-disease
#17
Junghee Lee, Yunha Kim, Tian Liu, Yu Jin Hwang, Seung Jae Hyeon, Hyeonjoo Im, Kyungeun Lee, Victor E Alvarez, Ann C McKee, Soo-Jong Um, Manwook Hur, Inhee Mook-Jung, Neil W Kowall, Hoon Ryu
Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Despite decades of study, effective treatments for AD are lacking. Mitochondrial dysfunction has been closely linked to the pathogenesis of AD, but the relationship between mitochondrial pathology and neuronal damage is poorly understood. Sirtuins (SIRT, silent mating type information regulation 2 homolog in yeast) are NAD-dependent histone deacetylases involved in aging and longevity. The objective of this study was to investigate the relationship between SIRT3 and mitochondrial function and neuronal activity in AD...
February 2018: Aging Cell
https://www.readbyqxmd.com/read/29118323/valproic-acid-sensitizes-hepatocellular-carcinoma-cells-to-proton-therapy-by-suppressing-nrf2-activation
#18
Jeong Il Yu, Changhoon Choi, Sung-Won Shin, Arang Son, Ga-Haeng Lee, Shin-Yeong Kim, Hee Chul Park
Although efficacy of combined histone deacetylase (HDAC) inhibitors and conventional photon radiotherapy is being tested in clinical trials, their combined effect with proton beam radiotherapy has yet to be determined. Here, we compared combined effect of valproic acid (VPA), a class I and II HDAC inhibitor and antiepileptic drug with proton and photon irradiation in hepatocellular carcinoma (HCC) cells in vitro and in vivo. We found that VPA sensitized more Hep3B cells to proton than to photon irradiation...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29117711/acetylation-regulates-thioredoxin-reductase-oligomerization-and-activity
#19
David E Wright, Zaid Altaany, Yumin Bi, Zaccary Alperstein, Patrick O'Donoghue
AIMS: Thioredoxin reductase 1 (TrxR1) is a cancer target and essential selenoprotein that defends the cell against reactive oxygen species and regulates cellular signaling and redox pathways. Previous cell-based studies correlated TrxR1 acetylation with modulated cellular reduction activity, yet the function of specific acetylation sites on TrxR1 remains unknown. INNOVATION: We produced site-specifically acetylated TrxR1 variants that also contain selenocysteine (Sec)...
December 14, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29096636/sodium-butyrate-promotes-apoptosis-in-breast-cancer-cells-through-reactive-oxygen-species-ros-formation-and-mitochondrial-impairment
#20
Vahid Salimi, Zahra Shahsavari, Banafsheh Safizadeh, Ameinh Hosseini, Narges Khademian, Masoumeh Tavakoli-Yaraki
BACKGROUND: Sodium butyrate (NaBu) is a short-chain fatty acid which serves as a histon deacetylase inhibitor and has received considerable interest as a possible regulator of cancer cell death. The regulatory effect of NaBu on cancer cell growth or death has yet to be illustrated in many cancers including breast cancer. This study is aimed to elucidate the possible effect of NaBu on regulation of breast cancer growth and apoptosis. METHODS: The cytotoxic effect of NaBu on the growth of breast cancer cells (MCF-7 and MDA-MB-468) and normal breast cells (MCF-10A) was determined using MTT assay...
November 2, 2017: Lipids in Health and Disease
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