scholarly journals HDAC2 Regulates Glial Cell Activation in Ischemic Mouse Retina

2019 ◽  
Vol 20 (20) ◽  
pp. 5159 ◽  
Author(s):  
Mi Sun Sung ◽  
Hwan Heo ◽  
Gwang Hyeon Eom ◽  
So Young Kim ◽  
Helong Piao ◽  
...  
Keyword(s):  
Mouse Model ◽  
Histone Acetylation ◽  
Glial Cells ◽  
Histone Deacetylases ◽  
Cell Activation ◽  
Ganglion Cells ◽  
Trichostatin A ◽  
Ischemia Reperfusion ◽  
Glial Activation ◽  
Mouse Retina

The current study was undertaken to investigate whether histone deacetylases (HDACs) can modulate the viability of retinal ganglion cells (RGCs) and the activity of glial cells in a mouse model of retinal ischemia-reperfusion (IR) injury. C57BL/6J mice were subjected to constant elevation of intraocular pressure for 60 min to induce retinal IR injury. Expression of macroglial and microglial cell markers (GFAP and Iba1), hypoxia inducing factor (HIF)-1α, and histone acetylation was analyzed after IR injury. To investigate the role of HDACs in the activation of glial cells, overexpression of HDAC1 and HDAC2 isoforms was performed. To determine the effect of HDAC inhibition on RGC survival, trichostatin-A (TSA, 2.5 mg/kg) was injected intraperitoneally. After IR injury, retinal GFAP, Iba1, and HIF-1α were upregulated. Conversely, retinal histone acetylation was downregulated. Notably, adenoviral-induced overexpression of HDAC2 enhanced glial activation following IR injury, whereas overexpression of HDAC1 did not significantly affect glial activation. TSA treatment significantly increased RGC survival after IR injury. Our results suggest that increased activity of HDAC2 is closely related to glial activation in a mouse model of retinal IR injury and inhibition of HDACs by TSA showed neuroprotective potential in retinas with IR injuries.

scholarly journals Panton-Valentine Leucocidin Proves Direct Neuronal Targeting and Its Early Neuronal and Glial Impacts a Rabbit Retinal Explant Model

Toxins ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 455 ◽  
Author(s):  
XuanLi Liu ◽  
Michel J Roux ◽  
Serge Picaud ◽  
Daniel Keller ◽  
Arnaud Sauer ◽  
...  
Keyword(s):  
Cell Activation ◽  
Ganglion Cells ◽  
Glial Activation ◽  
Inflammatory Factors ◽  
In Vivo Model ◽  
Suitable Model ◽  
Dependent Manner ◽  
Retinal Explants ◽  
Glial Changes

: Panton-Valentine leukocidin (PVL) retinal intoxication induces glial activation and inflammatory response via the interaction with retinal neurons. In this study, rabbit retinal explant was used as a model to study neuronal and glial consequences of PVL intoxication. Retinal explants were treated with different concentrations of PVL. PVL location and neuronal and glial changes were examined using immunohistochemistry. Some inflammatory factors were quantified using RT-qPCR at 4 and 8 h. These results were compared with those of control explants. PVL co-localized rapidly with retinal ganglion cells and with horizontal cells. PVL induced Müller and microglial cell activation. Retinal structure was altered and some amacrine and microglial cells underwent apoptosis. Glial activation and cell apoptosis increased in a PVL concentration- and time-dependent manner. IL-6 and IL-8 expression increased in PVL-treated explants but less than in control explants, which may indicate that other factors were responsible for glial activation and retinal apoptosis. On retinal explants, PVL co-localized with neuronal cells and induced glial activation together with microglial apoptosis, which confirms previous results observed in in vivo model. Rabbit retinal explant seems to be suitable model to further study the process of PVL leading to glial activation and retinal cells apoptosis.

scholarly journals AGL15 Controls the Embryogenic Reprogramming of Somatic Cells in Arabidopsis through the Histone Acetylation-Mediated Repression of the miRNA Biogenesis Genes

2020 ◽  
Vol 21 (18) ◽  
pp. 6733
Author(s):  
Katarzyna Nowak ◽  
Joanna Morończyk ◽  
Anna Wójcik ◽  
Małgorzata D. Gaj
Keyword(s):  
Histone Acetylation ◽  
Histone Deacetylases ◽  
Trichostatin A ◽  
Somatic Cells ◽  
Regulatory Function ◽  
Mirna Biogenesis ◽  
Embryogenic Culture ◽  
Cell Transcriptome ◽  
The Impact ◽  
Embryogenic Transition

The embryogenic transition of somatic cells requires an extensive reprogramming of the cell transcriptome. Relevantly, the extensive modulation of the genes that have a regulatory function, in particular the genes encoding the transcription factors (TFs) and miRNAs, have been indicated as controlling somatic embryogenesis (SE) that is induced in vitro in the somatic cells of plants. Identifying the regulatory relationships between the TFs and miRNAs during SE induction is of central importance for understanding the complex regulatory interplay that fine-tunes a cell transcriptome during the embryogenic transition. Hence, here, we analysed the regulatory relationships between AGL15 (AGAMOUS-LIKE 15) TF and miR156 in an embryogenic culture of Arabidopsis. Both AGL15 and miR156 control SE induction and AGL15 has been reported to target the MIR156 genes in planta. The results showed that AGL15 contributes to the regulation of miR156 in an embryogenic culture at two levels that involve the activation of the MIR156 transcription and the containment of the abundance of mature miR156 by repressing the miRNA biogenesis genes DCL1 (DICER-LIKE1), SERRATE and HEN1 (HUA-ENHANCER1). To repress the miRNA biogenesis genes AGL15 seems to co-operate with the TOPLESS co-repressors (TPL and TPR1-4), which are components of the SIN3/HDAC silencing complex. The impact of TSA (trichostatin A), an inhibitor of the HDAC histone deacetylases, on the expression of the miRNA biogenesis genes together with the ChIP results implies that histone deacetylation is involved in the AGL15-mediated repression of miRNA processing. The results indicate that HDAC6 and HDAC19 histone deacetylases might co-operate with AGL15 in silencing the complex that controls the abundance of miR156 during embryogenic induction. This study provides new evidence about the histone acetylation-mediated control of the miRNA pathways during the embryogenic reprogramming of plant somatic cells and the essential role of AGL15 in this regulatory mechanism.

scholarly journals Circadian and Light-Induced Transcription of Clock Gene Per1 Depends on Histone Acetylation and Deacetylation

2004 ◽  
Vol 24 (14) ◽  
pp. 6278-6287 ◽  
Author(s):  
Yoshihisa Naruse ◽  
Kentaro Oh-hashi ◽  
Norio Iijima ◽  
Midori Naruse ◽  
Hideyo Yoshioka ◽  
...  
Keyword(s):  
Histone Acetylation ◽  
Histone Deacetylases ◽  
Feedback Loop ◽  
Clock Gene ◽  
Clock Genes ◽  
Trichostatin A ◽  
Chromatin Modification ◽  
Histone Acetyltransferases ◽  
Fibroblast Cells ◽  
Circadian Clock Genes

ABSTRACT Circadian clock genes are regulated through a transcriptional-translational feedback loop. Alterations of the chromatin structure by histone acetyltransferases and histone deacetylases (HDACs) are commonly implicated in the regulation of gene transcription. However, little is known about the transcriptional regulation of mammalian clock genes by chromatin modification. Here, we show that the state of acetylated histones fluctuated in parallel with the rhythm of mouse Per1 (mPer1) or mPer2 expression in fibroblast cells and liver. Mouse CRY1 (mCRY1) repressed transcription with HDACs and mSin3B, which was relieved by the HDAC inhibitor trichostatin A (TSA). In turn, TSA induced endogenous mPer1 expression as well as the acetylation of histones H3 and H4, which interacted with the mPer1 promoter region in fibroblast cells. Moreover, a light pulse stimulated rapid histone acetylation associated with the promoters of mPer1 or mPer2 in the suprachiasmatic nucleus (SCN) and the binding of phospho-CREB in the CRE of mPer1. We also showed that TSA administration into the lateral ventricle induced mPer1 and mPer2 expression in the SCN. Taken together, these data indicate that the rhythmic transcription and light induction of clock genes are regulated by histone acetylation and deacetylation.

scholarly journals Wilson disease: intersecting DNA methylation and histone acetylation regulation of gene expression in a mouse model of hepatic copper accumulation

2021 ◽  
Author(s):  
Gaurav V. Sarode ◽  
Kari Neier ◽  
Noreene M. Shibata ◽  
Yuanjun Shen ◽  
Dmitry A Goncharov ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Mouse Model ◽  
Histone Acetylation ◽  
Wilson Disease ◽  
Metabolic Pathways ◽  
Histone Deacetylases ◽  
Copper Accumulation ◽  
Copper Transporter ◽  
Pathogenic Variants

AbstractThe pathogenesis of Wilson disease (WD) is multi-factorial, involving hepatic and brain copper accumulation due to pathogenic variants affecting the ATP7B gene and downstream epigenetic and metabolic mechanisms. Prior DNA methylation investigations in human WD liver and blood and in a WD mouse model revealed an epigenetic signature of WD, including alterations in the histone deacetylase HDAC5. To test the hypothesis that histone acetylation is altered with respect to copper overload and aberrant DNA methylation in WD, we investigated class IIa histone deacetylases (HDAC4 and HDAC5) and H3K9/H3K27 histone acetylation in the Jackson Laboratory toxic milk (tx-j) mouse model of WD compared to C3HeB/FeJ (C3H) control in response to 3 treatments: 60% kcal fat diet (HFD), D-penicillamine (PCA, copper chelator), and choline (methyl group donor). HDAC5 levels significantly increased in 9-week tx-j livers after 8 days of HFD compared to chow. In 24-week tx-j livers, HDAC4/5 levels were reduced 5- to 10-fold compared to C3H likely through mechanisms involving HDAC phosphorylation. HDAC4/5 levels were also affected by disease progression and accompanied by increased acetylation. PCA and choline partially restored HDAC4, HDAC5, H3K9ac, and H3K27ac levels to that of CH3 liver. Integrated RNA and chromatin immunoprecipitation sequencing analyses revealed genes regulating energy metabolism and cellular stress/development were, in turn, regulated by histone acetylation in tx-j mice compared to C3H, with Pparα and Pparγ among the most relevant targets. These results suggest dietary modulation of class IIa HDAC4/5, and subsequent H3K9/H3K27 acetylation/deacetylation, can regulate gene expression in key metabolic pathways in the pathogenesis of WD.Significance StatementWilson disease is considered a monogenic disease caused by pathogenic variants in the ATP7B copper transporter, resulting in hepatic and brain copper accumulation. Given the lack of genotype-phenotype correlation, evidence of epigenetic and metabolic mechanisms regulating phenotype in patients and in animal models could explain the high phenotype variability observed in WD. In this study, we identify class IIa histone deacetylases as players involved in the epigenetic regulation of key metabolic pathways that can affect WD severity as well as targets sensitive to dietary modulations, which is an important characteristic for designing effective and feasible therapies. Understanding the epigenetic mechanisms in WD pathogenesis contributes to a better understanding of the phenotypic variability in WD and other common liver conditions.

Kinetic analysis of histone acetylation turnover and Trichostatin A induced hyper- and hypoacetylation in alfalfa

2002 ◽  
Vol 80 (3) ◽  
pp. 279-293 ◽  
Author(s):  
Jakob H Waterborg ◽  
Tamás Kapros
Keyword(s):  
Gene Expression ◽  
Steady State ◽  
Histone Acetylation ◽  
Histone Deacetylases ◽  
Trichostatin A ◽  
Similar Rate ◽  
Lysine Methylation ◽  
Histone H2a ◽  
Turnover Rates

Dynamic histone acetylation is a characteristic of chromatin transcription. The first estimates for the rate of acetylation turnover of plants are reported, measured in alfalfa cells by pulse, pulse-chase, and steady-state acetylation labeling. Acetylation turnover half-lives of about 0.5 h were observed by all methods used for histones H3, H4, and H2B. This is consistent with the rate at which changes in gene expression occur in plants. Treatment with histone deacetylase inhibitor Trichostatin A (TSA) induced hyperacetylation at a similar rate. Replacement histone variant H3.2, preferentially localized in highly acetylated chromatin, displayed faster acetyl turnover. Histone H2A with a low level of acetylation was not subject to rapid turnover or hyperacetylation. Patterns of acetate labeling revealed fundamental differences between histone H3 versus histones H4 and H2B. In H3, acetylation of all molecules, limited by lysine methylation, had similar rates, independent of the level of lysine acetylation. Acetylation of histones H4 and H2B was seen in only a fraction of all molecules and involved multiacetylation. Acetylation turnover rates increased from mono- to penta- and hexaacetylated forms, respectively. TSA was an effective inhibitor of alfalfa histone deacetylases in vivo and caused a doubling in steady-state acetylation levels by 4–6 h after addition. However, hyperacetylation was transient due to loss of TSA inhibition. TSA-induced overexpression of cellular deacetylase activity produced hypoacetylation by 18 h treatment with enhanced acetate turnover labeling of alfalfa histones. Thus, application of TSA to change gene expression in vivo in plants may have unexpected consequences.

Trichostatin A inducesTrypanosoma cruzihistone and tubulin acetylation: effects on cell division and microtubule cytoskeleton remodelling

Parasitology ◽  
2018 ◽  
Vol 146 (4) ◽  
pp. 543-552 ◽  
Author(s):  
Jean de Oliveira Santos ◽  
Aline Araujo Zuma ◽  
Francisca Nathalia de Luna Vitorino ◽  
Julia Pinheiro Chagas da Cunha ◽  
Wanderley de Souza ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Histone Acetylation ◽  
Histone Deacetylases ◽  
Cell Biology ◽  
Trichostatin A ◽  
Hdac Inhibitors ◽  
Health Concern ◽  
Microtubule Cytoskeleton ◽  
Chromatin Compaction ◽  
Tubulin Acetylation

AbstractTrypanosoma cruzi, the causative agent of Chagas disease, is a public health concern in Latin America. Epigenetic events, such as histone acetylation, affect DNA topology, replication and gene expression. Histone deacetylases (HDACs) are involved in chromatin compaction and post-translational modifications of cytoplasmic proteins, such as tubulin. HDAC inhibitors, like trichostatin A (TSA), inhibit tumour cell proliferation and promotes ultrastructural modifications. In the present study, TSA effects on cell proliferation, viability, cell cycle and ultrastructure were evaluated, as well as on histone acetylation and tubulin expression of theT. cruziepimastigote form. Protozoa proliferation and viability were reduced after treatment with TSA. Quantitative proteomic analyses revealed an increase in histone acetylation after 72 h of TSA treatment. Surprisingly, results obtained by different microscopy methodologies indicate that TSA does not affect chromatin compaction, but alters microtubule cytoskeleton dynamics and impair kDNA segregation, generating polynucleated cells with atypical morphology. Confocal fluorescence microscopy and flow cytometry assays indicated that treated cell microtubules were more intensely acetylated. Increases in tubulin acetylation may be directly related to the higher number of parasites in the G2/M phase after TSA treatment. Taken together, these results suggest that deacetylase inhibitors represent excellent tools for understanding trypanosomatid cell biology.

scholarly journals Interplay between Müller cells and microglia aggravates retinal inflammatory response in experimental glaucoma

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xin Hu ◽  
Guo-Li Zhao ◽  
Meng-Xi Xu ◽  
Han Zhou ◽  
Fang Li ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Glial Cells ◽  
Cell Activation ◽  
Ganglion Cells ◽  
Müller Cells ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Inflammatory Factors ◽  
Muller Cells ◽  
Protein Levels ◽  
Experimental Glaucoma

Abstract Background Glaucoma, the leading cause of irreversible blindness, is a retinal neurodegenerative disease, which results from progressive apoptotic death of retinal ganglion cells (RGCs). Although the mechanisms underlying RGC apoptosis in glaucoma are extremely complicated, an abnormal cross-talk between retinal glial cells and RGCs is generally thought to be involved. However, how interaction of Müller cells and microglia, two types of glial cells, contributes to RGC injury is largely unknown. Methods A mouse chronic ocular hypertension (COH) experimental glaucoma model was produced. Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction (q-PCR), transwell co-culture of glial cells, flow cytometry assay, ELISA, Ca2+ image, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) techniques were employed to investigate the interaction of Müller cells and microglia, and its underlying mechanisms in COH retina. Results We first showed that Müller cell activation in mice with COH induced microglia activation through the ATP/P2X7 receptor pathway. The activation of microglia resulted in a significant increase in mRNA and protein levels of pro-inflammatory factors, such as tumor necrosis factor-α and interleukin-6. These inflammatory factors in turn caused the up-regulation of mRNA expression of pro-inflammatory factors in Müller cells through a positive feedback manner. Conclusions These findings provide robust evidence, for the first time, that retinal inflammatory response may be aggravated by an interplay between activated two types of glial cells. These results also suggest that to reduce the interplay between Müller cells and microglia could be a potential effective strategy for preventing the loss of RGCs in glaucoma.

scholarly journals Suppression of Excessive Histone Deacetylases Activity in Diabetic Hearts Attenuates Myocardial Ischemia/Reperfusion Injury via Mitochondria Apoptosis Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Yang Wu ◽  
Yan Leng ◽  
Qingtao Meng ◽  
Rui Xue ◽  
Bo Zhao ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Ischemia ◽  
Histone Deacetylases ◽  
Mitochondrial Permeability Transition ◽  
Apoptotic Cell ◽  
Trichostatin A ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Apoptosis Pathway ◽  
Myocardial Ischemia Reperfusion

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. H9C2 cardiomyocytes were exposed to high glucose for 24 h, followed by 4 h of hypoxia and 2 h of reoxygenation (H/R). Results. Both MI/R injury and diabetes mellitus elevated myocardium HDACs activity. MI/R induced apoptotic cell death was significantly decreased in diabetic rats treated with HDACs inhibitor trichostatin A (TSA). TSA administration markedly moderated dissipation of mitochondrial membrane potential, protected the integrity of mitochondrial permeability transition pore (mPTP), and decreased cell apoptosis. Notably, cotreatment with Akt inhibitor partly or absolutely inhibited the protective effect of TSA in vivo and in vitro. Furthermore, TSA administration activated Akt/Foxo3a pathway, leading to Foxo3a cytoplasm translocation and attenuation proapoptosis protein Bim expression. Conclusions. Both diabetes mellitus and MI/R injury increased cardiac HDACs activity. Suppression of HDACs activity triggered protective effects against MI/R and H/R injury under hyperglycemia conditions through Akt-modulated mitochondrial apoptotic pathways via Foxo3a/Bim.

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