scholarly journals Histone Deacetylase 1 and Sirtuin 1 Expression in Psoriatic Skin: A Comparison between Guttate and Plaque Psoriasis

Life ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 157
Author(s):  
Young-Ji Hwang ◽  
Jung-Im Na ◽  
Sang-Young Byun ◽  
Soon-Hyo Kwon ◽  
Seung-Hye Yang ◽  
...  
Keyword(s):  
Plaque Psoriasis ◽  
Histone Deacetylases ◽  
Basal Layer ◽  
Sirtuin 1 ◽  
Nuclear Antigen ◽  
Psoriatic Skin ◽  
Clinical Phenotypes ◽  
Histone Deacetylase 1 ◽  
Proliferative Markers ◽  
Guttate Psoriasis

Abnormal histone modification by histone deacetylases (HDACs), including HDAC1 and sirtuin 1 (SIRT1), has been reported to play an important role in the pathogenesis of psoriasis by altering cell proliferation, differentiation, and inflammation. However, findings on the expression level of HDACs in psoriatic skin lack consistency. We assessed the expression of HDAC1, SIRT1, p63, and proliferating cell nuclear antigen (PCNA) in skin tissues from 23 patients with psoriasis (15 with plaque psoriasis and eight with guttate psoriasis) and five healthy individuals using immunohistochemistry, and analyzed their associations with clinical phenotypes of the disease. The expression of HDAC1 and keratinocyte proliferative markers, such as p63 and PCNA significantly increased, whereas that of SIRT1 decreased in the basal layer (p < 0.05) of the patients with psoriasis compared to those in healthy controls. Among the patients with psoriasis, expression of HDAC1, p63, and PCNA was significantly higher in plaque psoriasis than in guttate psoriasis. There was no significant differences in the level of SIRT1 between the two clinical phenotypes. The findings of this study suggest that histone modifications are involved in the pathogenesis of psoriasis and may contribute to the formation of clinical phenotypes.

scholarly journals In vitro maturation affects chromosome segregation, spindle morphology and acetylation of lysine 16 on histone H4 in horse oocytes

2017 ◽  
Vol 29 (4) ◽  
pp. 721 ◽  
Author(s):  
Federica Franciosi ◽  
Ghylene Goudet ◽  
Irene Tessaro ◽  
Pascal Papillier ◽  
Rozenn Dalbies-Tran ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Histone Deacetylases ◽  
In Vitro Maturation ◽  
Sirtuin 1 ◽  
Histone H4 ◽  
Histone Deacetylase 1 ◽  
Dependent Protein ◽  
H4k16 Acetylation ◽  
Ovulatory Follicles

Implantation failure and genetic developmental disabilities in mammals are caused by errors in chromosome segregation originating mainly in the oocyte during meiosis I. Some conditions, like maternal ageing or in vitro maturation (IVM), increase the incidence of oocyte aneuploidy. Here oocytes from adult mares were used to investigate oocyte maturation in a monovulatory species. Experiments were conducted to compare: (1) the incidence of aneuploidy, (2) the morphology of the spindle, (3) the acetylation of lysine 16 on histone H4 (H4K16) and (4) the relative amount of histone acetyltransferase 1 (HAT1), K(lysine) acetyltransferase 8 (KAT8, also known as MYST1), histone deacetylase 1 (HDAC1) and NAD-dependent protein deacetylase sirtuin 1 (SIRT1) mRNA in metaphase II stage oocytes that were in vitro matured or collected from peri-ovulatory follicles. The frequency of aneuploidy and anomalies in spindle morphology was increased following IVM, along with a decrease in H4K16 acetylation that was in agreement with our previous observations. However, differences in the amount of the transcripts investigated were not detected. These results suggest that the degradation of transcripts encoding for histone deacetylases and acetyltransferases is not involved in the changes of H4K16 acetylation observed following IVM, while translational or post-translational mechanisms might have a role. Our study also suggests that epigenetic instabilities introduced by IVM may affect the oocyte and embryo genetic stability.

Histone deacetylase 1 regulates the malignancy of oral cancer cells via miR-154-5p/PCNA axis

2020 ◽  
Vol 401 (11) ◽  
pp. 1273-1281
Author(s):  
Yuanjing Lv ◽  
Jinle Lu ◽  
Xin Liu ◽  
Susheng Miao ◽  
Xionghui Mao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Histone Deacetylases ◽  
Specific Inhibitor ◽  
Nuclear Antigen ◽  
Over Expression ◽  
Histone Deacetylase 1 ◽  
Oral Cancer Cells ◽  
Targeted Inhibition

AbstractHistone deacetylases (HDACs) can regulate the progression of various cancers, while their roles in oral cancer cells are not well known. Our present study found that the HDAC1 was over expressed in oral squamous cell carcinoma (OSCC) cells and tissues. Targeted inhibition of HDAC1 via its specific inhibitor PCI24781 or siRNA can inhibit the proliferation of OSCC cells and increase their sensitivity to the chemo-sensitivity such as doxorubicin treatment. HDAC1 can regulate the expression of proliferating cell nuclear antigen (PCNA) via decreasing its mRNA stability. While over expression of PCNA can attenuate HDAC1 inhibition induced suppression of cell proliferation. We checked the expression of various miRNAs which can target the 3′UTR of PCNA. Results showed that HDAC1 can negative regulate the expression of miR-154-5p, inhibitor of miR-154-5p can attenuate PCI24781 treatment decreased PCNA expression and cell proliferation. Collectively, our present study suggested that HDAC1 can promote the growth and progression of OSCC via regulation of miR-154-5p/PCNA signals.

Interpretable SMILES-based QSAR model of inhibitory activity of sirtuins 1 and 2

2020 ◽  
Vol 23 ◽  
Author(s):  
Apilak Worachartcheewan ◽  
Alla P. Toropova ◽  
Andrey A. Toropov ◽  
Reny Pratiwi ◽  
Virapong Prachayasittikul ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Rational Design ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Sirtuin 1 ◽  
Data Set ◽  
Functional Roles ◽  
Molecular Features ◽  
Oecd Principles ◽  
Qsar Models

Background: Sirtuin 1 (Sirt1) and sirtuin 2 (Sirt2) are NAD+ -dependent histone deacetylases which play important functional roles in removal of the acetyl group of acetyl-lysine substrates. Considering the dysregulation of Sirt1 and Sirt2 as etiological causes of diseases, Sirt1 and Sirt2 are lucrative target proteins for treatment, thus there has been great interest in the development of Sirt1 and Sirt2 inhibitors. Objective: This study compiled the bioactivity data of Sirt1 and Sirt2 for the construction of quantitative structure-activity relationship (QSAR) models in accordance with the OECD principles. Method: Simplified molecular input line entry system (SMILES)-based molecular descriptors were used to characterize the molecular features of inhibitors while the Monte Carlo method of the CORAL software was employed for multivariate analysis. The data set was subjected to 3 random splits in which each split separated the data into 4 subsets consisting of training, invisible training, calibration and external sets. Results: Statistical indices for the evaluation of QSAR models suggested good statistical quality for models of Sirt1 and Sirt2 inhibitors. Furthermore, mechanistic interpretation of molecular substructures that are responsible for modulating the bioactivity (i.e. promoters of increase or decrease of bioactivity) was extracted via the analysis of correlation weights. It exhibited molecular features involved Sirt1 and Sirt2 inhibitors. Conclusion: It is anticipated that QSAR models presented herein can be useful as guidelines in the rational design of potential Sirt1 and Sirt2 inhibitors for the treatment of Sirtuin-related diseases.

scholarly journals Neuroprotection by Histone Deacetylase-Related Protein

2006 ◽  
Vol 26 (9) ◽  
pp. 3550-3564 ◽  
Author(s):  
Brad E. Morrison ◽  
Nazanin Majdzadeh ◽  
Xiaoguang Zhang ◽  
Aaron Lyles ◽  
Rhonda Bassel-Duby ◽  
...  
Keyword(s):  
Cell Death ◽  
Histone Deacetylase ◽  
Neuronal Death ◽  
Histone Deacetylases ◽  
Essential Feature ◽  
Gene Promoter ◽  
Related Protein ◽  
Phosphatidylinositol 3 Kinase ◽  
Histone Deacetylase 1 ◽  
H3 Acetylation

ABSTRACT The expression of histone deacetylase-related protein (HDRP) is reduced in neurons undergoing apoptosis. Forced reduction of HDRP expression in healthy neurons by treatment with antisense oligonucleotides also induces cell death. Likewise, neurons cultured from mice lacking HDRP are more vulnerable to cell death. Adenovirally mediated expression of HDRP prevents neuronal death, showing that HDRP is a neuroprotective protein. Neuroprotection by forced expression of HDRP is not accompanied by activation of the phosphatidylinositol 3-kinase-Akt or Raf-MEK-ERK signaling pathway, and treatment with pharmacological inhibitors of these pathways fails to inhibit the neuroprotection by HDRP. Stimulation of c-Jun phosphorylation and expression, an essential feature of neuronal death, is prevented by HDRP. We found that HDRP associates with c-Jun N-terminal kinase (JNK) and inhibits its activity, thus explaining the inhibition of c-Jun phosphorylation by HDRP. HDRP also interacts with histone deacetylase 1 (HDAC1) and recruits it to the c-Jun gene promoter, resulting in an inhibition of histone H3 acetylation at the c-Jun promoter. Although HDRP lacks intrinsic deacetylase activity, treatment with pharmacological inhibitors of histone deacetylases induces apoptosis even in the presence of ectopically expressed HDRP, underscoring the importance of c-Jun promoter deacetylation by HDRP-HDAC1 in HDRP-mediated neuroprotection. Our results suggest that neuroprotection by HDRP is mediated by the inhibition of c-Jun through its interaction with JNK and HDAC1.

Recent advances in chalcone-based anticancer heterocycles: A structural and molecular target perspective

2021 ◽  
Vol 28 ◽  
Author(s):  
Vishal Kumar ◽  
Sanjeev Dhawan ◽  
Pankaj Sanjay Girase ◽  
Paul Awolade ◽  
Suraj Raosaheb Shinde ◽  
...  
Keyword(s):  
Histone Deacetylases ◽  
Biological Activities ◽  
Molecular Targets ◽  
Cathepsin K ◽  
Cost Effective ◽  
Sirtuin 1 ◽  
Anticancer Activities ◽  
Structural Variations ◽  
Research Attention ◽  
Endothelial Growth Factor

: Chalcones are an interesting class of compounds endowed with a plethora of biological activities beneficial to human health. These chemo types have continued to attract increased research attention over the years; hence, numerous natural and synthetic chalcones have found with interesting anticancer activities through the inhibition of various molecular targets including ABCG2, BCRP, P-glycoprotein, 5α-reductase, Androgen receptor (AR), Histone deacetylases (HDAC), Sirtuin 1, proteasome, Vascular endothelial growth factor (VEGF), Cathepsin-K, tubulin, CDC25B phosphatase, Topoisomerase, EBV, NF-κB, mTOR, BRAF and Wnt/β-catenin. Moreover, the study of intrinsic mechanisms of action, particularly relating to specific cellular pathways and modes of engagement with molecular targets, may help medicinal chemists to develop a more effective, selective, and cost-effective chalcone-based anticancer drugs. This review, therefore, sheds light on the effect of structural variations on the anticancer potency of chalcone hybrids reported in 2018-2019 alongside their mechanism of action, molecular targets, and potential impacts on effective cancer chemotherapy.

scholarly journals Effects of a 10% carbamide peroxide bleaching agent on rat oral epithelium proliferation

2002 ◽  
Vol 13 (3) ◽  
pp. 162-165 ◽  
Author(s):  
Rodrigo de Castro Albuquerque ◽  
Ricardo Santiago Gomez ◽  
Rodrigo Aliprandi Dutra ◽  
Wallison Arthuso Vasconcellos ◽  
Renato Santiago Gomez ◽  
...  
Keyword(s):  
Oral Mucosa ◽  
Topical Application ◽  
Basal Layer ◽  
Nuclear Antigen ◽  
Oral Epithelium ◽  
Basal Cells ◽  
Immunohistochemical Expression ◽  
Carbamide Peroxide ◽  
Peroxide Bleaching ◽  
Short Course

The purpose of the present study was to evaluate the influence of short course topical application of carbamide peroxide on proliferating cell nuclear antigen (PCNA) immunohistochemical expression in the oral tongue mucosa of rats. Twelve male Wistar rats were submitted to topical application of 10% carbamide peroxide on one side of the dorsal tongue once a week for three consecutive weeks. Only distilled water was applied on the control side. The animals were killed on days 0, 10, and 20 after the last application. The tongue was fixed in buffered formalin for 24 h and embedded in paraffin. Tissue blocks (3 µm) were subjected to the biotin-streptavidin amplified system for identification of PCNA. The percentage of epithelial-positive basal cells in each side of the tongue mucosa was calculated. The results demonstrated that topical application of 10% carbamide peroxide increases PCNA immunohistochemical expression on the basal layer of the oral mucosa epithelium of rats on day 0 after treatment. In conclusion, short-course use of carbamide peroxide induces transient epithelial cell proliferation of the oral mucosa of rats.

scholarly journals Histone deacetylase 1 reduces NO production in endothelial cells via lysine deacetylation of NO synthase 3

2014 ◽  
Vol 307 (5) ◽  
pp. H803-H809 ◽  
Author(s):  
Kelly A. Hyndman ◽  
Dao H. Ho ◽  
Martiana F. Sega ◽  
Jennifer S. Pollock
Keyword(s):  
Endothelial Cells ◽  
Histone Deacetylases ◽  
Production Control ◽  
No Synthase ◽  
No Production ◽  
Lysine Acetylation ◽  
Nonhistone Proteins ◽  
Endothelin 1 ◽  
Histone Deacetylase 1 ◽  
Nitrite Production

The lysine acetylation state of nonhistone proteins may be regulated through histone deacetylases (HDACs). Evidence suggests that nitric oxide (NO) synthase 3 (NOS3; endothelial NOS) is posttranslationally lysine acetylated, leading to increased NO production in the endothelium. We tested the hypothesis that NOS3 is lysine acetylated and that upregulated HDAC1-mediated deacetylation leads to reduced NO production in endothelial cells. We determined that NOS3 is basally lysine acetylated in cultured bovine aortic endothelial cells (BAECs). In BAECs, HDAC1 is expressed in the nucleus and cytosol and forms a novel protein-protein interaction with NOS3. Overexpression of HDAC1 in BAECs resulted in a significant reduction in NOS3 lysine acetylation (control = 1.0 ± 0.1 and HDAC1 = 0.59 ± 0.08 arbitrary units, P < 0.01) and significantly blunted basal nitrite production (control 287.7 ± 29.1 and HDAC1 172.4 ± 31.7 pmol·mg−1·h−1, P < 0.05) as well as attenuating endothelin-1-stimulated nitrite production (control = 481.8 ± 50.3 and HDAC1 243.1 ± 48.2 pmol·mg−1·h−1, P < 0.05). While HDAC1 knockdown with small-interfering RNA resulted in no change in NOS3 acetylation level, yet increased basal nitrite production (730.6 ± 99.1 pmol·mg−1·h−1) and further exaggerated increases in endothelin-1 stimulated nitrite production (1276.9 ± 288.2 pmol·mg−1·h−1) was observed. Moreover, overexpression or knockdown of HDAC1 resulted in no significant effect on NOS3 protein expression or NOS3 phosphorylation sites T497, S635, or S1179. Thus these data indicate that upregulated HDAC1 decreases NOS3 activity, most likely through direct lysine deacetylation of NOS3. We propose that HDAC1-mediated deacetylation of NOS3 may represent a novel target for endothelial dysfunction.

scholarly journals Selective impact of MeCP2 and associated histone deacetylases on the dynamics of evoked excitatory neurotransmission

2011 ◽  
Vol 106 (1) ◽  
pp. 193-201 ◽  
Author(s):  
Erika D. Nelson ◽  
Manjot Bal ◽  
Ege T. Kavalali ◽  
Lisa M. Monteggia
Keyword(s):  
Histone Deacetylases ◽  
Hippocampal Neurons ◽  
Autism Spectrum ◽  
Synaptic Activity ◽  
Short Term ◽  
Histone Deacetylase 1 ◽  
Inhibitory Neurotransmission ◽  
Presynaptic Release ◽  
Excitatory Neurotransmission ◽  
Excitatory Drive

An imbalance between the strengths of excitatory and inhibitory synaptic inputs has been proposed as the cellular basis of autism and related neurodevelopmental disorders. Previous studies examining spontaneous levels of excitatory and inhibitory neurotransmission in the forebrain regions of methyl-CpG-binding protein 2 ( Mecp2) mutant mice, models of the autism spectrum disorder Rett syndrome, have identified a decrease in excitatory drive, in some cases coupled with an increase in inhibitory synaptic strength, as a major source of this imbalance. Here, we reevaluated this question by examining the short-term dynamics of evoked neurotransmission between hippocampal neurons cultured from MeCP2 knockout mice and found a marked increase in evoked excitatory neurotransmission that is consistent with an increase in presynaptic release probability. This increase in evoked excitatory drive was not matched with alterations in evoked inhibitory neurotransmission. Moreover, we observed similar excitatory drive specific changes after the loss of key histone deacetylases (histone deacetylase 1 and 2) that form a complex with MeCP2 and mediate transcriptional regulation. These findings suggest a distinct role for MeCP2 and its cofactors in the regulation of evoked excitatory neurotransmission compared with their essential role in basal synaptic activity.

scholarly journals Sirtuin 1 (SIRT1)

2011 ◽  
Vol 16 (10) ◽  
pp. 1153-1169 ◽  
Author(s):  
Walter Stünkel ◽  
Robert M. Campbell
Keyword(s):  
Histone Deacetylases ◽  
Cellular Systems ◽  
Sirtuin 1 ◽  
Model Systems ◽  
New Concepts ◽  
Specific Tumor ◽  
Recent Developments ◽  
Context Specific ◽  
Shed Light ◽  
Sirt1 Activator

The sirtuin family of NAD-dependent histone deacetylases (HDACs) consists of seven mammalian proteins, SIRT1–7. Many of the sirtuin isoforms also deacetylate nonhistone substrates, such as p53 (SIRT1) and α-tubulin (SIRT2). The sirtuin literature focuses on pharmacological activators of SIRT1 (e.g., resveratrol, SRT1720), proposed as therapeutics for diabetes, neurodegeneration, inflammation, and others. However, many of the SIRT1 activator results may have been due to artifacts in the assay methodology (i.e., use of fluorescently tagged substrates). A biological role for SIRT1 in cancer has been given less scrutiny but is no less equivocal. Although proposed initially as an oncogene, we present herein compelling data suggesting that SIRT1 is indeed a context-specific tumor suppressor. For oncology, SIRT1 inhibitors (dual SIRT1/2) are indicated as potential therapeutics. A number of sirtuin inhibitors have been developed but with mixed results in cellular systems and animal models. It is unclear whether this has been due to poorly understood model systems, signalling redundancy, and/or inadequately potent and selective tool compounds. This review provides an overview of recent developments in the field of SIRT1 function. While focusing on oncology, it aims to shed light on new concepts of expanding the selectivity spectrum, including other sirtuins such as SIRT2.

The Brigham Scalp Nail Inverse Palmoplantar Psoriasis Composite Index (B-SNIPI): A Novel Index to Measure All Non-plaque Psoriasis Subsets

2014 ◽  
Vol 41 (6) ◽  
pp. 1230-1232 ◽  
Author(s):  
Mital Patel ◽  
Stephanie W. Liu ◽  
Abrar Qureshi ◽  
Joseph F. Merola
Keyword(s):  
Plaque Psoriasis ◽  
Composite Index ◽  
Objective Measure ◽  
Severity Index ◽  
Chronic Inflammatory Disease ◽  
Response To Treatment ◽  
Psoriatic Skin ◽  
Patient Reported ◽  
Significant Impairment

Psoriasis is a chronic inflammatory disease that encompasses a large spectrum of clinically distinct subtypes. Although chronic plaque psoriasis is reported as the most common form of psoriatic skin disease, there is growing evidence that other variants including scalp, nail, inverse, and palmoplantar psoriasis are prevalent, undertreated, and associated with significant impairment in quality of life. Currently, the Psoriasis Area and Severity Index (PASI) is the standard to assess psoriasis severity as well as response to treatment; however, the PASI has several limitations. In response to this need and as a complementary objective measure to the PASI, we created the Brigham Scalp Nail Inverse Palmoplantar Psoriasis Composite Index (B-SNIPI), based on patient-surveyed, patient-reported outcomes equally weighted with physician assessment of disease activity. Herein we summarize the B-SNIPI as presented at the 2013 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

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