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Aindrila Chatterjee, Janine Seyfferth, Jacopo Lucci, Ralf Gilsbach, Sebastian Preissl, Lena Böttinger, Christoph U Mårtensson, Amol Panhale, Thomas Stehle, Oliver Kretz, Abdullah H Sahyoun, Sergiy Avilov, Stefan Eimer, Lutz Hein, Nikolaus Pfanner, Thomas Becker, Asifa Akhtar
A functional crosstalk between epigenetic regulators and metabolic control could provide a mechanism to adapt cellular responses to environmental cues. We report that the well-known nuclear MYST family acetyl transferase MOF and a subset of its non-specific lethal complex partners reside in mitochondria. MOF regulates oxidative phosphorylation by controlling expression of respiratory genes from both nuclear and mtDNA in aerobically respiring cells. MOF binds mtDNA, and this binding is dependent on KANSL3. The mitochondrial pool of MOF, but not a catalytically deficient mutant, rescues respiratory and mtDNA transcriptional defects triggered by the absence of MOF...
October 20, 2016: Cell
Jiachao Zhang, Qisong Hu, Chuanbiao Xu, Sixin Liu, Congfa Li
Pepper pericarp microbiota plays an important role in the pepper peeling process for the production of white pepper. We collected pepper samples at different peeling time points from Hainan Province, China, and used a metagenomic approach to identify changes in the pericarp microbiota based on functional gene analysis. UniFrac distance-based principal coordinates analysis revealed significant changes in the pericarp microbiota structure during peeling, which were attributed to increases in bacteria from the genera Selenomonas and Prevotella...
2016: PloS One
E Faghihloo, Y Araei, M Mohammadi, H Mirzaei, H R Mohammadi, T Mokhtari-Azad
Gastric cancer is among the leading causes of cancer-related death, and the symptoms are commonly characterized in advanced stages. Histone acetylation is among the most important epigenetic alterations occurring during cancer development. In addition, reduced E-cadherin expression is a major contributor in the process of tumor cell invasion and metastasis. Oxamflatin is a histone deacetylase inhibitor that has been suggested as a promising anti-tumor agent; yet its effect on the viability and invasion of gastric tumor cells is unclear...
October 21, 2016: Cancer Gene Therapy
Nicole Mons, Daniel Beracochea
A prime mechanism that contributes to the development and maintenance of alcoholism is the dysregulation of the hypothalamic-pituitary-adrenal axis activity and the release of glucocorticoids (cortisol in humans and primates, corticosterone in rodents) from the adrenal glands. In the brain, sustained, local elevation of glucocorticoid concentration even long after cessation of chronic alcohol consumption compromises functional integrity of a circuit, including the prefrontal cortex (PFC), the hippocampus (HPC), and the amygdala (AMG)...
2016: Frontiers in Psychiatry
E H Baker, S W Levin, Z Zhang, A B Mukherjee
BACKGROUND AND PURPOSE: Infantile neuronal ceroid lipofuscinosis is a devastating neurodegenerative storage disease caused by palmitoyl-protein thioesterase 1 deficiency, which impairs degradation of palmitoylated proteins (constituents of ceroid) by lysosomal hydrolases. Consequent lysosomal ceroid accumulation leads to neuronal injury, resulting in rapid neurodegeneration and childhood death. As part of a project studying the treatment benefits of a combination of cysteamine bitartrate and N-acetyl cysteine, we made serial measurements of patients' brain volumes with MR imaging...
October 20, 2016: AJNR. American Journal of Neuroradiology
R Gajendra Reddy, Lenin Veeraval, Swati Maitra, Marylène Chollet-Krugler, Sophie Tomasi, Françoise Lohézic-Le Dévéhat, Joël Boustie, Sumana Chakravarty
BACKGROUND: Natural products from lichens are widely investigated for their biological properties, yet their potential as central nervous system (CNS) therapeutic agents is less explored. PURPOSE: The present study investigated the neuroactive properties of selected lichen compounds (atranorin, perlatolic acid, physodic acid and usnic acid), for their neurotrophic, neurogenic and acetylcholine esterase (AChE) activities. METHODS: Neurotrophic activity (neurite outgrowth) was determined using murine neuroblastoma Neuro2A cells...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Zi Lin, Zheng-Feng Wu, Cui-Hua Jiang, Qing-Wen Zhang, Sheng Ouyang, Chun-Tao Che, Jian Zhang, Zhi-Qi Yin
BACKGROUND: Hepatic steatosis (HS) is the early stage of nonalcoholic fatty liver disease which is caused by impaired hepatic lipid homeostasis. Cyclocarya paliurus, an herbal tea consumed in China, has been demonstrated to ameliorate abnormal lipid metabolism for the treatment of metabolic diseases. PURPOSE: We aimed to investigate the regulative effect of chloroform extract from Cyclocarya paliurus (ChE) on treatment of HS, as well as key factors involved in hepatic lipid metabolism...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Claudio Bazzi, Tomoko Usui, Virginia Rizza, Daniela Casellato, Maurizio Gallieni, Masaomi Nangaku
BACKGROUND: The clinical course of idiopathic membranous nephropathy (IMN) varies from spontaneous remission of nephrotic syndrome (NS) to end-stage renal disease (ESRD). Selecting patients with high risk of progression for immunosuppressive therapy is mandatory. METHODS: 86 IMN subjects were followed for median of 69 months (range 6-253). Receiver operating characteristic curve and Cox proportional hazards model were used to evaluate prognostic factors for progression, defined as ESRD or eGFR reduction ≥50% of baseline...
October 20, 2016: Nephrology
Rui Su, Jia-Nan Gong, Ming-Tai Chen, Li Song, Chao Shen, Xin-Hua Zhang, Xiao-Lin Yin, Hong-Mei Ning, Bing Liu, Fang Wang, Yan-Ni Ma, Hua-Lu Zhao, Jia Yu, Jun-Wu Zhang
Aberrant activation of c-Myc plays an important oncogenic role via regulating a series of coding and non-coding genes in acute myeloid leukemia (AML). Histone deacetylases (HDACs) can remove acetyl group from histone and regulate gene expression via changing chromatin structure. Here, we found miR-451 is abnormally down-regulated in AML patient samples; c-Myc recruits HDAC3 to form a transcriptional suppressor complex, co-localizes on the miR-451 promoter, epigenetically inhibits its transcription and finally induces its downregulation in AML...
October 15, 2016: Oncotarget
Jawed Iqbal, Mairaj Ahmed Ansari, Binod Kumar, Dipanjan Dutta, Arunava Roy, Leela Chikoti, Gina Pisano, Sujoy Dutta, Shahrooz Vahedi, Mohanan Valiya Veettil, Bala Chandran
IFI16 (gamma-interferon-inducible protein 16), a predominantly nuclear protein involved in transcriptional regulation, also functions as an innate immune response DNA sensor and induces the IL-1β and antiviral type-1 interferon-β (IFN-β) cytokines. We have shown that IFI16, in association with BRCA1, functions as a sequence independent nuclear sensor of episomal dsDNA genomes of KSHV, EBV and HSV-1. Recognition of these herpesvirus genomes resulted in IFI16 acetylation, BRCA1-IFI16-ASC-procaspase-1 inflammasome formation, cytoplasmic translocation, and IL-1β generation...
October 2016: PLoS Pathogens
Kishore Polireddy, Ruochen Dong, Peter R McDonald, Tao Wang, Brendan Luke, Ping Chen, Melinda Broward, Anuradha Roy, Qi Chen
BACKGROUND: Pancreatic cancer has an enrichment of stem-like cancer cells (CSCs) that contribute to chemoresistant tumors prone to metastasis and recurrence. Drug screening assays based on cytotoxicity cannot identify specific CSC inhibitors, because CSCs comprise only a small portion of cancer cell population, and it is difficult to propagate stable CSC populations in vitro for high-throughput screening (HTS) assays. Based on the important role of cancer cell epithelial-to-mesenchymal transition (EMT) in promoting CSCs, we hypothesized that inhibition of EMT can be a useful strategy for inhibiting CSCs, and therefore a feasible approach for HTS can be built for identification of CSC inhibitors, based on assays detecting EMT inhibition...
2016: PloS One
Xin Gu, Bingjie Gu, Xianhui Lv, Zhenzhen Yu, Rong Wang, Xiaoli Zhou, Wanxin Qiao, Zhiyuan Mao, Guoping Zuo, Qing Li, Dengshun Miao, Jianliang Jin
Impaired apoptosis of fibroblast-like synoviocytes (FLSs) causes synovial hyperplasia, facilitating destruction of cartilage and bone in rheumatoid arthritis (RA). Tumor necrosis factor (TNF)-α, a dominant inflammatory mediator in RA pathogenesis, promotes progression of RA symptoms. Prevalence of 1, 25-dihydroxy-vitamin D3 (hereafter termed VD) deficiency is 30-63% in patients with RA. Whether VD leads to apoptosis or enhances TNF-α-mediated apoptosis in FLSs to ameliorate RA is unclear. To determine this, 10-week-old CYP27B1-deficient (CYP27B1(-/-)) mice with collagen-induced arthritis (CIA) were intraperitoneally treated with 1 μg/kg VD every other day for 9 weeks...
October 20, 2016: Cell Death & Disease
Raquel Fonseca, Rui A Carvalho, Cristina Lemos, Ana C Sequeira, Inês R Pita, Fábio Carvalho, Carlos D Silva, Rui D S Prediger, Ivana Jarak, Rodrigo A Cunha, Carlos A Fontes Ribeiro, Attila Köfalvi, Frederico C Pereira
INTRODUCTION: We recently showed that a single high dose of methamphetamine (METH) induces a persistent frontal cortical monoamine depletion that is accompanied by helpless-like behavior in mice. However, brain metabolic alterations underlying both neurochemical and mood alterations remain unknown. AIMS: Herein, we aimed at characterizing frontal cortical metabolic alterations associated with early negative mood behavior triggered by METH. Adult C57BL/6 mice were injected with METH (30 mg/kg, i...
October 19, 2016: CNS Neuroscience & Therapeutics
Tobias Wagner, Maren Godmann, Thorsten Heinzel
Histone deacetylases (HDACs) are controlling dynamic protein acetylation by removing acetyl moieties from lysine. Histone deacetylases themselves are regulated on the posttranslational level, including modifications with small ubiquitin-like modifier (SUMO) proteins. Detecting SUMO modifications of deacetylases by immunoblotting is technically challenging due to the typically low ratio of the modified compared to the unmodified species. Here, we describe a set of methods for the detection of endogenous sumoylated HDACs by immunoprecipitation and immunoblotting techniques...
2017: Methods in Molecular Biology
Martin Wieczorek, Karl-Heinz Gührs, Thorsten Heinzel
Posttranslational acetylation of lysine residues has been discovered as multifaceted regulatory modification for various nuclear, cytoplasmic, and mitochondrial proteins. The implementation of high-resolution and high-throughput mass spectrometry (MS) approaches has led to the identification of a hitherto underappreciated, large number of acetylation sites for a broad spectrum of cellular proteins. In this chapter, we describe a comprehensive protocol for the purification of an in vivo-acetylated, ectopically expressed, FLAG-epitope tagged nonhistone protein through immunoprecipitation (IP)...
2017: Methods in Molecular Biology
Jan Hagenbucher, Hilda Stekman, Alfonso Rodriguez-Gil, Michael Kracht, M Lienhard Schmitz
The family of seven-in-absentia (SIAH) ubiquitin E3 ligases functions in the control of numerous key signaling pathways. These enzymes belong to the RING (really interesting new gene) group of E3 ligases and mediate the attachment of ubiquitin chains to substrates, which then leads to their proteasomal degradation. Here, we describe a protocol that allows measuring SIAH-mediated ubiquitination and degradation of its client proteins as exemplified by acetyl transferases using simple overexpression experiments...
2017: Methods in Molecular Biology
Jing Jiao, Rongxiang Han, Wayne W Hancock, Ulf H Beier
Determining protein acetylation by immunoprecipitation and immunoblotting can be challenging, especially if the tissue of interest is low in quantity, and when good quality acetylation site-specific antibodies are not available. Proximity ligation assays allow a sensitive and quantitative method to assess Foxp3 acetylation in regulatory T cells, with as little as 1.5 × 10(5) cells within two days turnaround time. This method is of potential use in other similar scenarios, when post-translational modifications of a protein of interest need to be determined with only a small amount of sample and in the absence of specific antibodies that can assess the post-translational modification in the protein of interest...
2017: Methods in Molecular Biology
Sophia Pinz, Anne Rascle
Transcriptional activation by STAT5 is repressed by deacetylase inhibitors. Investigating the role of deacetylases (HDACs) in STAT5-mediated transcription implies the analysis of molecular events taking place at the chromatin level. We describe here two alternative methods of chromatin immunoprecipitation that allow the characterization of chromatin modifications ensuing STAT5 activation and its inhibition by deacetylase inhibitors, in particular changes in histone acetylation, in histone occupancy, and in the association/dissociation of transcription factors and other chromatin-associated factors...
2017: Methods in Molecular Biology
David Olagnier, Cindy Chiang, John Hiscott
The dynamics of chromatin structure contribute to the regulation of gene transcription and in part, the changes in chromatin structure associated with gene activation/repression are a function of the state of histone acetylation. Histone deacetylases (HDACs) deacetylate histone tails leading to a more compact structure of chromatin that in turn represses gene transcription. Given the rapid activation and/or repression of gene networks following microbial infection, the role of HDACs in the epigenetic regulation of genes involved in the innate and adaptive immune responses has become an area of extensive research...
2017: Methods in Molecular Biology
Thierry Buchou, Minjia Tan, Sophie Barral, Anne-Laure Vitte, Sophie Rousseaux, Juan Arechaga, Saadi Khochbin
Isolation of pools of spermatogenic cells at specific developmental stages is essential for the investigations of molecular events controlling critical transitions during spermatogenesis. Large-scale cell purification techniques allow for combined proteomics, genomics, and transcriptomics studies. Herein, we describe a procedure for the purification of meiotic and post-meiotic male germ cells from adult mouse testes. We also describe how the fractionated cell populations could be used for further studies. In our laboratory, these protocols are routinely used to specifically investigate the molecular basis of histone acetylation/acylation-driven epigenetic programming...
2017: Methods in Molecular Biology
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