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histone deacetylase stroke

Radhika Patnala, Thiruma V Arumugam, Neelima Gupta, S Thameem Dheen
Cerebral ischemia leads to neuroinflammation and activation of microglia which further contribute to stroke pathology. Understanding regulation of microglial activation will aid in the development of therapeutic strategies that mitigate microglia-mediated neurotoxicity in neuropathologies, including ischemia. In this study, we investigated the epigenetic regulation of microglial activation by studying histone modification histone 3-lysine 9-acetylation (H3K9ac) and its regulation by histone deacetylase (HDAC) inhibitors...
October 8, 2016: Molecular Neurobiology
Sumana Chakravarty, Priya Jhelum, Unis Ahmad Bhat, Wenson D Rajan, Swati Maitra, Salil S Pathak, Anant B Patel, Arvind Kumar
Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. Therapeutic interventions to minimize ischemia-induced neural damage are limited due to poor understanding of molecular mechanisms mediating complex pathophysiology in stroke. Recently, epigenetic mechanisms mostly histone lysine (K) acetylation and deacetylation have been implicated in ischemic brain damage and have expanded the dimensions of potential therapeutic intervention to the systemic/ local administration of histone deacetylase inhibitors...
September 21, 2016: Biochimica et Biophysica Acta
Zhenhua Han, Xin Dong, Chaoying Zhang, Yue Wu, Zuyi Yuan, Xinhong Wang
Recent genome-wide association studies (GWAS) have indicated an association of histone deacetylase 9 (HDAC9) genetic variant with large-vessel stroke and coronary artery disease, among the European population. However, whether HDAC9 gene is associated with an increased susceptibility to acute coronary syndrome (ACS) in Chinese Han population is not known. A total of 472 patients, including patients with ACS (N = 309), and those with chest pain syndrome (controls, N = 163) were enrolled. Genotyping for HDAC9 gene was performed using the ligation detection reaction assay...
2016: BioMed Research International
Malgorzata Ziemka-Nalecz, Joanna Jaworska, Joanna Sypecka, Rafał Polowy, Robert K Filipkowski, Teresa Zalewska
Neonatal hypoxic-ischemic (HI) injury still remains an important issue as it is a major cause of neonatal death and neurological dysfunctions. Currently, there are no well-established treatments to reduce brain damage and its long-term sequel in infants. Recently, reported data show that histone deacetylase inhibitors provide neuroprotection in adult stroke models. However, the proof of their relevance in vivo after neonatal HI brain injury remains particularly limited. In the present study, we show neuroprotective/neurogenic effect of sodium butyrate (SB), one of histone deacetylase inhibitors (HDACis), in the dentate gyrus of HI-injured immature rats...
August 30, 2016: Molecular Neurobiology
Dietrich A Ruess, Moriz Probst, Goran Marjanovic, Uwe A Wittel, Ulrich T Hopt, Tobias Keck, Dirk Bausch
BACKGROUND: Histone deacetylases (HDAC) catalyze N-terminal deacetylation of lysine-residues on histones and multiple nuclear and cytoplasmic proteins. In various animal models, such as trauma/hemorrhagic shock, ischemic stroke or myocardial infarction, HDAC inhibitor (HDACi) application is cyto- and organoprotective and promotes survival. HDACi reduce stress signaling, cell death and inflammation. Hepatic ischemia-reperfusion (I/R) injury during major liver resection or transplantation increases morbidity and mortality...
2016: PloS One
Xue-Bin Wang, Ya-di Han, Shrestha Sabina, Ning-Hua Cui, Shuai Zhang, Ze-Jin Liu, Cong Li, Fang Zheng
A previous genome-wide association study showed that a single nucleotide polymorphism (SNP) rs2107595 in histone deacetylase 9 (HDAC9) gene was associated with large artery stroke (LAS) in Caucasians. Based on the similar atherosclerotic pathogenesis between LAS and coronary artery disease (CAD), we aimed to evaluate the associations of SNP rs2107595 with CAD risk and the severity of coronary atherosclerosis in a Chinese Han population, and explore the potential gene-environment interactions among SNP rs2107595 and conventional CAD risk factors...
2016: PloS One
Hsin-Da Tsai, Jui-Sheng Wu, Mei-Han Kao, Jin-Jer Chen, Grace Y Sun, Wei-Yi Ong, Teng-Nan Lin
Many population-based epidemiological studies have unveiled an inverse correlation between intake of herbal plants and incidence of stroke. C. nutans is a traditional herbal medicine widely used for snake bite, viral infection and cancer in Asian countries. However, its role in protecting stroke damage remains to be studied. Despite of growing evidence to support epigenetic regulation in the pathogenesis and recovery of stroke, a clear understanding of the underlying molecular mechanisms is still lacking. In the present study, primary cortical neurons were subjected to in vitro oxygen-glucose deprivation (OGD)-reoxygenation and hypoxic neuronal death was used to investigate the interaction between C...
September 2016: Neuromolecular Medicine
Fen Xue, Jin-Wen Huang, Pei-Yan Ding, Hong-Gang Zang, Zhi-Jian Kou, Ting Li, Juan Fan, Zheng-Wu Peng, Wen-Jun Yan
Sirtuin 1 (Sirt1) is a class III histone deacetylase involved in neuroprotection induced by hyperbaric oxygen preconditioning (HBO-PC) in animal models of ischemia. However, the underlying mechanisms remain to be illustrated. In the present study, rats exposed to middle cerebral artery occlusion (MCAO) were used to establish an ischemic stroke model. The infarct volume ratio, neurobehavioral score, and expressions of Sirt1, nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and superoxide dismutase 1 (SOD1) were evaluated at 7 days after reperfusion, and the level of malondialdehyde (MDA) was used to assess oxidative stress...
August 1, 2016: Behavioural Brain Research
Haifa Kassis, Amjad Shehadah, Chao Li, Yi Zhang, Yisheng Cui, Cynthia Roberts, Neema Sadry, Xianshuang Liu, Michael Chopp, Zheng Gang Zhang
We have previously demonstrated that stroke induces nuclear shuttling of class IIa histone deacetylase 4 (HDAC4). Stroke-induced nuclear shuttling of HDAC4 is positively and significantly correlated with improved indices of neuronal remodeling in the peri-infarct cortex. In this study, using a rat model for middle cerebral artery occlusion (MCAO), we tested the effects of selective inhibition of class IIa HDACs on functional recovery and neuronal remodeling when administered 24hr after stroke. Adult male Wistar rats (n = 15-17/group) were subjected to 2 h MCAO and orally gavaged with MC1568 (a selective class IIa HDAC inhibitor), SAHA (a non-selective HDAC inhibitor), or vehicle-control for 7 days starting 24 h after MCAO...
June 2016: Neurochemistry International
Xiaofei Meng, Jin Tan, Mengmeng Li, Shuling Song, Yuyang Miao, Qiang Zhang
Silent information regulator factor 2-related enzyme 1 (sirtuin 1, Sirt1) is a nicotinamide adenine dinucleotide-dependent deacetylase, which can deacetylate histone and non-histone proteins and other transcription factors, and is involved in the regulation of many physiological functions, including cell senescence, gene transcription, energy balance, and oxidative stress. Ischemia/hypoxia injury remains an unresolved and complicated situation in the diseases of ischemia stroke, heart failure, and coronary heart disease, especially among the old folks...
March 14, 2016: Cellular and Molecular Neurobiology
Hui Yuan, Kyle Denton, Lin Liu, Xue-Jun Li, Sharon Benashski, Louise McCullough, Jun Li
Mounting evidence suggests that epigenetic modifications play critical roles in the survival/death of stressed neurons. Chief among these modifications is the deacetylation of histones within the chromatin by histone deacetylases (HDACs). HDAC4 is highly expressed in neurons and is usually trapped in cytosol. However, tightly regulated signal-dependent shuttling of this molecule between cytosol and nucleus occurs. Here, we studied the intracellular trafficking of HDAC4 and regulatory mechanisms during stroke...
July 2016: Neurobiology of Disease
Zhiping Hu, Bingwu Zhong, Jieqiong Tan, Chunli Chen, Qiang Lei, Liuwang Zeng
Despite great progresses in the treatment and prevention of ischemic stroke, it is still among the leading causes of death and serious long-term disability all over the world, indicating that innovative neural regenerative and neuroprotective agents are urgently needed for the development of therapeutic approaches with greater efficacy for ischemic stroke. More and more evidence suggests that a spectrum of epigenetic processes play an important role in the pathophysiology of cerebral ischemia. In the present review, we first discuss recent developments in epigenetic mechanisms, especially their roles in the pathophysiology of cerebral ischemia...
February 19, 2016: Molecular Neurobiology
Weichen Shi, Xinbing Wei, Ziying Wang, Huirong Han, Yi Fu, Jiang Liu, Yan Zhang, Jian Guo, Chuanqiao Dong, Di Zhou, Quan Zhou, Yuxin Chen, Fan Yi
Histone deacetylase (HDAC) 9, a member of class II HDACs, regulates a wide variety of normal and abnormal physiological functions, which is usually expressed at high levels in the brain and skeletal muscle. Although studies have highlighted the importance of HDAC-mediated epigenetic processes in the development of ischaemic stroke and very recent genome-wide association studies have identified a variant in HDAC9 associated with large-vessel ischemic stroke, the molecular events by which HDAC9 induces cerebral injury keep unclear...
June 2016: Journal of Cellular and Molecular Medicine
Martina Olsson, Karin Hultman, Sylvie Dunoyer-Geindre, Maurice A Curtis, Richard L M Faull, Egbert K O Kruithof, Christina Jern
The serine protease tissue-type plasminogen activator (t-PA) is involved in both vital physiological brain processes, such as synaptic plasticity, and pathophysiological conditions, such as neurodegeneration and ischemic stroke. Recent data suggest that epigenetic mechanisms play an important role in the regulation of t-PA in human endothelial cells. However, there are limited data on epigenetic regulation of t-PA in human brain-derived cells. We demonstrate that treatment of cultured human neurons and human astrocytes with the histone deacetylase inhibitors trichostatin A (TSA) and MS-275 resulted in a two- to threefold increase in t-PA mRNA and protein expression levels...
2016: Gene Regulation and Systems Biology
Zhifei Wang, Yan Leng, Junyu Wang, Hsiao-Mei Liao, Joel Bergman, Peter Leeds, Alan Kozikowski, De-Maw Chuang
Histone deacetylase (HDAC) 6 exists exclusively in cytoplasm and deacetylates cytoplasmic proteins such as α-tubulin. HDAC6 dysfunction is associated with several pathological conditions in the central nervous system. This study investigated the beneficial effects of tubastatin A (TubA), a novel specific HDAC6 inhibitor, in a rat model of transient middle cerebral artery occlusion (MCAO) and an in vitro model of excitotoxicity. Post-ischemic TubA treatment robustly improved functional outcomes, reduced brain infarction, and ameliorated neuronal cell death in MCAO rats...
2016: Scientific Reports
Shabir Ahmad Ganai, Mahalakshmi Ramadoss, Vijayalakshmi Mahadevan
Epigenetic regulation of neuronal signalling through histone acetylation dictates transcription programs that govern neuronal memory, plasticity and learning paradigms. Histone Acetyl Transferases (HATs) and Histone Deacetylases (HDACs) are antagonistic enzymes that regulate gene expression through acetylation and deacetylation of histone proteins around which DNA is wrapped inside a eukaryotic cell nucleus. The epigenetic control of HDACs and the cellular imbalance between HATs and HDACs dictate disease states and have been implicated in muscular dystrophy, loss of memory, neurodegeneration and autistic disorders...
2016: Current Neuropharmacology
Valeria Conti, Maurizio Forte, Graziamaria Corbi, Giusy Russomanno, Luigi Formisano, Alessandro Landolfi, V Izzo, Amelia Filippell, Carmine Vecchione, Albino Carrizzo
The mammalian sirtuins (SIRT1-7) are NAD+ dependent deacetylases involved in aging and in a wide range of cellular functions by regulating histones and several transcription factors. SIRT1, the best-characterized member of the family, acts as sensor of stress to address the cells forwards an appropriate defense. A large body of evidence has showed that SIRT1 induces both cellular and systemic protective effects in the cardiovascular system by preventing stress-induced apoptosis and senescence and ameliorating the endothelial dysfunction...
October 18, 2015: Current Drug Targets
Guo Qingxu, Zhang Yan, Xu Jiannan, Liu Yunlong
Genome-wide association studies have demonstrated various polymorphisms of histone deacetylase 9 (HDAC9) gene was strong risk locus for large-vessel stroke, but the results were controversial. This study aims to replicate the association between the previous detected SNPs of HDAC9 and the susceptibility of ischemic stroke. The study population consisted of 262 consecutive patients diagnosed with ischemic stroke and 300 age and gender matched unrelated controls between October 2012 and October 2014. Rs11984041, rs2389995, and rs2240419 of HDAC9 were genotyped and compared between the cases and controls...
January 2016: Pathology Oncology Research: POR
Zheng Gang Zhang, Michael Chopp
Endogenous brain repair after stroke involves a set of highly interactive processes, such as angiogenesis, neurogenesis, oligodendrogenesis, synaptogenesis, and axonal outgrowth, which together orchestrate neurological recovery. During the past several years, there have been advances in our understanding of miRNAs and histone deacetylases (HDACs) in brain repair processes after stroke. Emerging data indicate the important role of exosomes for intercellular communication in promoting coupled brain remodeling processes...
September 2015: Trends in Molecular Medicine
Hongdi Lv, Ling Wang, Jinchang Shen, Shaojun Hao, Aimin Ming, Xidong Wang, Feng Su, Zhengchen Zhang
Silent information regulator 1 (SIRT1), a histone deacetylase, has been suggested to be effective in ischemic brain diseases. Salvianolic acid B (SalB) is a polyphenolic and one of the active components of Salvia miltiorrhiza Bunge. Previous studies suggested that SalB is protective against ischemic stroke. However, the role of SIRT1 in the protective effect of SalB against cerebral ischemia has not been explored. In this study, the rat brain was subjected to middle cerebral artery occlusion (MCAO). Before this surgery, rats were intraperitoneally administrated SalB with or without EX527, a specific SIRT1 inhibitor...
June 2015: Brain Research Bulletin
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