Disease relevance of Hdac1

• Histone deacetylase (HDAC) inhibitors are emerging as a new class of anticancer therapeutic agents and have been demonstrated to induce differentiation in some myeloid leukemia cell lines [1].
• Dose-dependent blockade to cardiomyocyte hypertrophy by histone deacetylase inhibitors [2].
• A therapeutic strategy uses histone deacetylase inhibitors to modulate the expression of genes involved in the pathogenesis of rheumatoid arthritis [3].
• Altogether, our results demonstrate that VPA is neuroprotective in the cerebral ischemia model and suggest that the protection mechanisms may involve HDAC inhibition and HSP induction [4].
• BACKGROUND/AIMS: Previously, trichostatin A (TSA), a histone deacetylase inhibitor, has been shown to exhibit strong antifibrotic characteristics in hepatic stellate cells (HSC), which are known to play a central role in chronic liver diseases [5].

Psychiatry related information on Hdac1

• Valproic acid (VPA), used to treat bipolar mood disorder and seizures, also inhibits histone deacetylase (HDAC) [6].

High impact information on Hdac1

• The action of valproic acid has been linked to both inositol depletion and to inhibition of histone deacetylase (HDAC) [7].
• Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila [8].
• During the first 10 postnatal days, administration of valproic acid (VPA), the specific inhibitor for histone deacetylase activity, resulted in significant hypomyelination with delayed expression of late differentiation markers and retained expression of progenitor markers [9].
• Our study provides the first evidence that a histone deacetylase is essential for unrestricted cell proliferation by repressing the expression of selective cell cycle inhibitors [10].
• A fraction of these differences in gene expression is reversible by either the histone deacetylase inhibitor TSA or the methyl donor l-methionine [11].

Chemical compound and disease context of Hdac1

• Valproic acid reduces brain damage induced by transient focal cerebral ischemia in rats: potential roles of histone deacetylase inhibition and heat shock protein induction [4].
• Cytoprotective effect of novel histone deacetylase inhibitors against polyglutamine toxicity [12].

Biological context of Hdac1

• Furthermore, acetylation of histones (induced by trichostatin A, a specific inhibitor of histone deacetylase) enhanced MIP-2 expression by cells stimulated with IL-1beta [13].
• Furthermore, in CEM-C7H2 cells, at higher concentrations of butyrate (5 - 10 mM) or trichostatin A (0.4 - 0.8 microM), there was a minor but reproducible antagonistic effect of dexamethasone on apoptosis induced by each of the two histone deacetylase inhibitors, suggesting that this antagonistic effect too, is related to histone hyperacetylation [14].
• In cells transfected with HNF-4alpha, short-chain fatty acids and trichostatin A, an inhibitor of histone deacetylase, synergistically enhanced promoter activity, suggesting that hyperacetylation of histones is an important component of the transactivation of the Glc-6-Pase gene promoter by HNF-4alpha [15].
• Furthermore, we observed that elevating levels of histone acetylation through the use of the histone deacetylase inhibitors trichostatin A or sodium butyrate enhanced induction of long term potentiation at Schaffer-collateral synapses in area CA1 of the hippocampus, a candidate mechanism contributing to long term memory formation in vivo [16].
• Inhibition of HDAC by trichostatin blocked the deacetylation of p53 and its transcriptional activity toward a reporter gene construct [17].

Anatomical context of Hdac1

• Epithelial cells transduce this signal through histone deacetylase, modulating the secretion of chemokines [13].
• Histone deacetylase inhibition-mediated neuronal differentiation of multipotent adult neural progenitor cells [18].
• NRSF associated with the transcriptional corepressor mSin3 and formed a complex with histone deacetylase (HDAC) in ventricular myocytes [19].
• In this study, we show that HDAC inhibitors have a novel action on osteoclast differentiation [1].
• The effect of 2 HDAC inhibitors, trichostatin A (TSA) and sodium butyrate (NaB), on osteoclastogenesis was investigated using rat and mouse bone marrow cultures and a murine macrophage cell line RAW264 [1].

Associations of Hdac1 with chemical compounds

• The fact that the non-additive relationship with dexamethasone for apoptosis induction was observed with both histone deacetylase inhibitors suggests that in thymocytes this phenomenon is related to histone acetylation [14].
• Here we report that the histone acetyltransferase Tip60 and the histone deacetylase HDAC7 interact with one of the ET receptors, ETA, as determined by yeast two-hybrid analysis, glutathione S-transferase pull-down assays, and co-immunoprecipitation from transfected COS-7 cells [20].
• Interestingly, we observed that histone deacetylase inhibitors, such as trichostatin A (TSA) and suberoylanilide hydroxamic acid, strongly potentiated the lipopolysaccharide (LPS)-induced inflammatory response in murine N9 and rat primary microglial cells as well in neural co-cultures and hippocampal slice cultures [21].
• Impact of novel histone deacetylase inhibitors, CHAP31 and FR901228 (FK228), on adenovirus-mediated transgene expression [22].
• We have previously reported the development of a nonisotopic assay for HDAC using a fluorescent derivative of epsilon-acetyl lysine [23].

Physical interactions of Hdac1

• Additionally Nkx2.2 recruited a histone deacetylase 1-mSin3A complex to the myelin basic protein promoter [24].
• MM-1 has been reported to repress the E-box-dependent transcription activity of c-Myc by recruiting histone deacetylase 1 complex via TIF1beta/KAP1 [25].

Regulatory relationships of Hdac1

• Inhibition of histone deacetylase suppresses osteoclastogenesis and bone destruction by inducing IFN-beta production [26].
• Calcium/calmodulin-dependent protein kinase activates serum response factor transcription activity by its dissociation from histone deacetylase, HDAC4. Implications in cardiac muscle gene regulation during hypertrophy [27].
• Endogenous alpha-synuclein is induced by valproic acid through histone deacetylase inhibition and participates in neuroprotection against glutamate-induced excitotoxicity [28].

Other interactions of Hdac1

• Thus, ras/ERK signaling pathway can be considered in chemotherapeutic strategies of NaBu regardless of its inhibitory action on histone deacetylase [29].
• Histone deacetylase inhibitors prevent oxidative neuronal death independent of expanded polyglutamine repeats via an Sp1-dependent pathway [30].
• The histone deacetylase inhibitor trichostatin A prevented and quickly reversed deacetylation of GluR2-associated histones [31].
• We then tested the role of histone deacetylase activity in cAMP activation of four of these genes (c-FOS, ICER, NOR-1, and NUR77) by treating cells with the histone deacetylase inhibitor trichostatin A [32].
• To this end, we studied the kinetics of serum-stimulated transcription of c-fos, c-jun, fra-1, egr-1, and cyclinD1 genes, as well as the effects of sodium butyrate, an inhibitor of histone deacetylase activity, on transcription of these genes in normal REF cells and transformants E1A+ras [33].

Analytical, diagnostic and therapeutic context of Hdac1

• Trichostatin A (TSA), a specific HDAC inhibitor, relieved NRSE-mediated repression of ANP promoter activity, and chromatin immunoprecipitation assays revealed the involvement of histone deacetylation in NRSE-mediated repression of ANP gene expression [19].
• Co-culture and slice culture experiments showed that the presence of astrocytes and neurones did not stimulate or prevent the pro-inflammatory potentiation induced by histone deacetylase inhibitor in microglial cells [21].
• Cardiac histones are substrates of histone deacetylase activity in hemorrhagic shock and resuscitation [34].
• HPLC fractions corresponding to trichostatin A and N-demethylated trichostatin A exhibited histone deacetylase-inhibitory activity; no other fractions were biologically active [35].
• Development of a liquid chromatography/electrospray tandem mass spectrometry assay for the quantification of apicidin, a novel histone deacetylase inhibitor, in rat serum: application to a pharmacokinetic study [36].

References