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https://www.readbyqxmd.com/read/29620443/mir-2861-behaves-as-a-biomarker-of-lung-cancer-stem-cells-and-regulates-the-hdac5-erk-system-genes
#1
Mengya Zhao, Lin Li, Jundong Zhou, Xueyuan Cui, Qingmei Tian, Yaqing Jin, Yimin Zhu
Cancer stem cells (CSCs) are responsible for cancer initiating, recurrence, and drug resistance. Discovery of novel biomarkers for CSCs is helpful for early diagnosis and prognosis. Lung cancer stem cells (LCSCs) were closely related to the occurrence and development of lung cancer. In our study, the important role of miR-2861 in maintaining the stemness of LCSCs was investigated. The LCSC differentiation model was established through introducing serum into the medium of H460 spheres. miR-2861 expression was significantly higher in LCSCs no matter compared to the differentiation cells or normal cells...
April 2018: Cellular Reprogramming
https://www.readbyqxmd.com/read/29610273/subcellular-compartmentalization-of-proximal-g%C3%AE-q-receptor-signaling-produces-unique-hypertrophic-phenotypes-in-adult-cardiac-myocytes
#2
Erika F Dahl, Steven C Wu, Chastity L Healy, Brian A Harsch, Gregory C Shearer, Timothy D O'Connell
G protein-coupled receptors that signal through Gαq (Gq receptors), such as α1-adrenergic receptors (α1-ARs) or angiotensin receptors, share a common proximal signaling pathway that activates phospholipase Cβ1 (PLCβ1), which cleaves phosphatidylinositol-4,5-bisphosphate (PIP2) to produce inositol-1,4,5-trisphosphate (IP3) and diacylglycerol. Despite these common proximal signaling mechanisms, Gq receptors produce distinct physiological responses, yet the mechanistic basis for this remains unclear. In the heart, Gq receptors are thought to induce myocyte hypertrophy through a mechanism termed excitation-transcription coupling, which provides a mechanistic basis for compartmentalization of calcium required for contraction versus IP3-dependent intranuclear calcium required for hypertrophy...
April 2, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29522762/bidirectional-regulation-of-hdac5-by-makap%C3%AE-signalosomes-in-cardiac-myocytes
#3
Kimberly L Dodge-Kafka, Moriah Gildart, Jinliang Li, Hrishikesh Thakur, Michael S Kapiloff
Class IIa histone deacetylases (HDACs) are transcriptional repressors whose nuclear export in the cardiac myocyte is associated with the induction of pathological gene expression and cardiac remodeling. Class IIa HDACs are regulated by multiple, functionally opposing post-translational modifications, including phosphorylation by protein kinase D (PKD) that promotes nuclear export and phosphorylation by protein kinase A (PKA) that promotes nuclear import. We have previously shown that the scaffold protein muscle A-kinase anchoring protein β (mAKAPβ) orchestrates signaling in the cardiac myocyte required for pathological cardiac remodeling, including serving as a scaffold for both PKD and PKA...
March 6, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29520168/the-antidepressant-action-of-3-2-carboxypiperazin-4-yl-propyl-1-phosphonic-acid-is-mediated-by-phosphorylation-of-histone-deacetylase-5
#4
Min Hyeop Park, Miyeon Choi, Yong-Seok Kim, Hyeon Son
3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, produces rapid antidepressant-like effects in animal models of depression. However, the molecular mechanisms underlying these behavioral actions remain unknown. Here, we demonstrate that CPP rapidly stimulates histone deacetylase (HDAC) 5 phosphorylation and nuclear export in rat hippocampal neurons. These effects are accompanied by calcium/calmodulin kinase II (CaMKII) and protein kinase D (PKD) phosphorylation...
March 2018: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/29472387/class-iia-histone-deacetylases-link-camp-signaling-to-the-myelin-transcriptional-program-of-schwann-cells
#5
Clara Gomis-Coloma, Sergio Velasco-Aviles, Jose A Gomez-Sanchez, Angeles Casillas-Bajo, Johannes Backs, Hugo Cabedo
Schwann cells respond to cyclic adenosine monophosphate (cAMP) halting proliferation and expressing myelin proteins. Here we show that cAMP signaling induces the nuclear shuttling of the class IIa histone deacetylase (HDAC)-4 in these cells, where it binds to the promoter and blocks the expression of c-Jun , a negative regulator of myelination. To do it, HDAC4 does not interfere with the transcriptional activity of MEF2. Instead, by interacting with NCoR1, it recruits HDAC3 and deacetylates histone 3 in the promoter of c-Jun , blocking gene expression...
February 22, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29448109/hdac1-regulates-the-stability-of-glutamate-carboxypeptidase-ii-protein-by-modulating-acetylation-status-of-lysine-479-residue
#6
Ji-Young Choi, Jun-Hyeok Ko, Sangmee Ahn Jo
Our previous study showed that the level of glutamate carboxypeptidase II (GCPII) protein is regulated by valproic acid, a histone deacetylase (HDAC) inhibitor, through acetylation of lysine residue in the GCPII protein in human astrocytes, U-87MG. The present study further investigated which HDAC subtype is involved in the acetylation of GCPII. The results revealed that GCPII interacted with HDAC1 but not with HDAC2, HDAC3, HDAC4, HDAC5, and HDAC6. Overexpression of catalytic domain (1-56 aa)-deleted HDAC1, which poorly binds to GCPII, enhanced lysine acetylation in GCPII and increased the level of GCPII protein when compared with that of the wild-type HDAC1...
February 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29447134/histone-deacetylase-5-hdac5-regulates-neuropathic-pain-through-sry-related-hmg-box-10-sox10-dependent-mechanism-in-mice
#7
Pan Gu, Zhiqiang Pan, Xiao-Min Wang, Liting Sun, Lydia Wai Tai, Chi Wai Cheung
A strong link between histone deacetylases (HDACs) and nociceptive hypersensitivity has been indicated in different pain models. However, the underlying molecular and cellular mechanisms remain elusive. Here, we discovered that partial sciatic nerve ligation-induced mechanical allodynia and thermal hyperalgesia in mice were associated with increased mRNA and protein expressions of HDAC5 (a member of class IIa HDACs) and SRY-related HMG-box 10 (SOX10) in the ipsilateral lumbar dorsal horn. Gene knockdown of spinal HDAC5 or SOX10 attenuated partial sciatic nerve ligation-induced nociceptive hypersensitivity, companied with decrease of spinal neuronal sensitization markers, namely phosphorylated-Erk, phosphorylated-GluN1 (ser896), and c-Fos...
March 2018: Pain
https://www.readbyqxmd.com/read/29397902/role-of-dorsal-striatum-histone-deacetylase-5-in-incubation-of-methamphetamine-craving
#8
Xuan Li, Maria B Carreria, Kailyn R Witonsky, Tamara Zeric, Olivia M Lofaro, Jennifer M Bossert, Jianjun Zhang, Felicia Surjono, Christopher T Richie, Brandon K Harvey, Hyeon Son, Christopher W Cowan, Eric J Nestler, Yavin Shaham
BACKGROUND: Methamphetamine (meth) seeking progressively increases after withdrawal (incubation of meth craving). We previously demonstrated an association between histone deacetylase 5 (HDAC5) gene expression in the rat dorsal striatum and incubation of meth craving. Here we used viral constructs to study the causal role of dorsal striatum HDAC5 in this incubation. METHODS: In experiment 1 (overexpression), we injected an adeno-associated virus bilaterally into dorsal striatum to express either green fluorescent protein (control) or a mutant form of HDAC5, which strongly localized to the nucleus...
December 29, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29396145/hdac5-regulates-the-formation-of-drug-memories
#9
Alexander C W Smith, Paul J Kenny
Cocaine-associated environmental cues can precipitate craving and relapse in addicted individuals even after years of abstinence, but the molecular mechanisms by which maladaptive drug memories are generated remain unclear. New findings suggest that histone deacetylase 5 (HDAC5) plays a key role in this process.
January 9, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29380950/sarcoplasmic-reticulum-ca2-induced-ca2-release-regulates-class-iia-hdac-localization-in-mouse-embryonic-cardiomyocytes
#10
Sari Karppinen, Sandra L Hänninen, Risto Rapila, Pasi Tavi
In embryonic cardiomyocytes, sarcoplasmic reticulum (SR)-derived Ca2+ release is required to induce Ca2+ oscillations for contraction and to control cardiac development through Ca2+ -activated pathways. Here, our aim was to study how SR Ca2+ release regulates cytosolic and nuclear Ca2+ distribution and the subsequent effects on the Ca2+ -dependent localization of class IIa histone deacetylases (HDAC) and cardiac-specific gene expression in embryonic cardiomyocytes. Confocal microscopy was used to study changes in Ca2+ -distribution and localization of immunolabeled HDAC4 and HDAC5 upon changes in SR Ca2+ release in mouse embryonic cardiomyocytes...
January 2018: Physiological Reports
https://www.readbyqxmd.com/read/29339432/deregulation-of-hdac5-by-viral-interferon-regulatory-factor-3-plays-an-essential-role-in-kaposi-s-sarcoma-associated-herpesvirus-induced-lymphangiogenesis
#11
Hye-Ra Lee, Fan Li, Un Yung Choi, Hye Ryun Yu, Grace M Aldrovandi, Pinghui Feng, Shou-Jiang Gao, Young-Kwon Hong, Jae U Jung
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi's sarcoma (KS), which is one of the most common HIV-associated neoplasms. The endothelium is the thin layer of squamous cells where vascular blood endothelial cells (BECs) line the interior surface of blood vessels and lymphatic endothelial cells (LECs) are in direct contact with lymphatic vessels. The KS lesions contain a prominent compartment of neoplastic spindle morphology cells that are closely related to LECs. Furthermore, while KSHV can infect both LECs and BECs in vitro , its infection activates genetic programming related to lymphatic endothelial cell fate, suggesting that lymphangiogenic pathways are involved in KSHV infection and malignancy...
January 16, 2018: MBio
https://www.readbyqxmd.com/read/29229738/hdac5-integrates-er-stress-and-fasting-signals-to-regulate-hepatic-fatty-acid-oxidation
#12
Xinchen Qiu, Jian Li, Sihan Lv, Jiamin Yu, Junkun Jiang, Jindong Yao, Yang Xiao, Bingxin Xu, Haiyan He, Fangfei Guo, Zhen-Ning Zhang, Chao Zhang, Bing Luan
Disregulation of fatty acid oxidation, one of the major mechanisms for maintaining hepatic lipid homeostasis under fasting conditions, leads to hepatic steatosis. Although obesity and type 2 diabetes-induced endoplasmic reticulum (ER) stress contribute to hepatic steatosis, it is largely unknown how ER stress regulates fatty acid oxidation. Here we show that fasting glucagon stimulates the dephosphorylation and nuclear translocation of histone deacetylase 5 (HDAC5), where it interacts with PPARα and promotes transcriptional activity of PPARα...
February 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29223407/stat3-mediated-epigenetic-silencing-of-foxp3-in-lada-t-cells-is-regulated-through-hdac5-and-dnmt1
#13
Can Hou, Yanjun Zhong, Zhen Wang, Zhao Ming, Gan Huang, Lin Ouyang, Yijun Li, Qianjin Lu, Zhiguang Zhou
In LADA patients, Tregs are reduced and FOXP3 is downregulated in CD4+ T cells, but the etiology remains unclear. Our study included in 20 LADA patients and 20 healthy control patients. qRT-PCR results showed that STAT3, HDAC3, HDAC5, SIRT1, DNMT1 and DNMT3b mRNAs were significantly upregulated in LADA CD4+ T cells than controls, while FOXP3 mRNA significantly decreased. p-STAT3, STAT3, DNMT1 and DNMT3b expressions were increased demonstrated by western blot. ChIP-PCR suggested that p-STAT3 binds to the Foxp3 promoter, meanwhile, histone H3 acetylation at K9 and K14 of FOXP3 promoter were significantly lower than controls...
December 6, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29212224/hadc5-deacetylates-mkl1-to-dampen-tnf-%C3%AE-induced-pro-inflammatory-gene-transcription-in-macrophages
#14
Zilong Li, Hao Qin, Jianfei Li, Liming Yu, Yuyu Yang, Yong Xu
Macrophage-dependent inflammatory response on the one hand functions as a key line of defense in host immunity but on the other hand underlies the pathogenesis of a host of human pathologies when aberrantly activated. Our previous investigations have led to the identification of megakaryocytic leukemia 1 (MKL1) as a key co-factor of NF-κB/p65 participating in TNF-α induced pro-inflammatory transcription in macrophages. How post-translational modifications contribute to the modulation of MKL1 activity remains an underexplored subject matter...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29199045/the-mechanism-of-myocardial-hypertrophy-regulated-by-the-interaction-between-mhrt-and-myocardin
#15
Ying Luo, Yao Xu, Chen Liang, Weibing Xing, Tongcun Zhang
As a strong transactivator of promoters containing CarG boxes, myocardin was critical for the cardiac muscle program and necessary for normal cardiogenesis. So it probably represents a viable therapeutic biomarker in the setting of cardiac hypertrophy and failure. In recent years, the studies of regulation of cardiac hypertrophy via myocardin are so common, and the molecular mechanism is becoming more and more clear. Here, we have revealed a kind of interaction between mhrt and myocardin shown as a feedback regulatory mechanism in the regulation of cardiac hypertrophy...
March 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29176673/phosphoproteomics-of-camp-signaling-of-bordetella-adenylate-cyclase-toxin-in-mouse-dendritic-cells
#16
Jakub Novák, Ivo Fabrik, Irena Linhartová, Marek Link, Ondřej Černý, Jiří Stulík, Peter Šebo
The adenylate cyclase toxin (CyaA) of the whooping cough agent Bordetella pertussis subverts immune functions of host myeloid cells expressing the αM β2 integrin (CD11b/CD18, CR3 or Mac-1). CyaA delivers into cytosol of cells an extremely catalytically active adenylyl cyclase enzyme, which disrupts the innate and adaptive immune functions of phagocytes through unregulated production of the key signaling molecule cAMP. We have used phosphoproteomics to analyze cAMP signaling of CyaA in murine bone marrow-derived dendritic cells...
November 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29164959/palmatine-attenuates-isoproterenol-induced-pathological-hypertrophy-via-selectively-inhibiting-hdac2-in-rats
#17
Yonggang Yuan, Wanzhong Peng, Yongxing Liu, Zesheng Xu
This study aimed to exploit the potential therapeutic value of palmatine in treatment of cardiac hypertrophy and the underlying molecular mechanism. Rat hypertrophy model was established by intraperitoneal isoproterenol (ISO) injection. The hypertrophy was evaluated with cardiac hypertrophic parameters, hemodynamic parameters, lipid profile, and non-specific cardiac markers. The animals were intraperitoneally administrated with either palmatine or vehicle. The relative expressions of ANP, BNP, HDAC2, HDAC5, KLF4, and INPP5F transcripts were determined by real-time polymerase chain reaction (PCR)...
December 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/29138868/hdac-inhibitor-lmk%C3%A2-235-promotes-the-odontoblast-differentiation-of-dental-pulp-cells
#18
Zhao Liu, Ting Chen, Qianqian Han, Ming Chen, Jie You, Fuchun Fang, Ling Peng, Buling Wu
The role of dental pulp cells (DPCs) in hard dental tissue regeneration had received increasing attention because DPCs can differentiate into odontoblasts and other tissue‑specific cells. In recent years, epigenetic modifications had been identified to serve an important role in cell differentiation, and histone deacetylase (HDAC) inhibitors have been widely studied by many researchers. However, the effects of HDAC4 and HDAC5 on the differentiation of DPCs and the precise molecular mechanisms remain unclear...
January 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29109977/prior-alcohol-use-enhances-vulnerability-to-compulsive-cocaine-self-administration-by-promoting-degradation-of-hdac4-and-hdac5
#19
Edmund A Griffin, Philippe A Melas, Royce Zhou, Yang Li, Peter Mercado, Kimberly A Kempadoo, Stacy Stephenson, Luca Colnaghi, Kathleen Taylor, Mei-Chen Hu, Eric R Kandel, Denise B Kandel
Addiction to cocaine is commonly preceded by experiences with legal or decriminalized drugs, such as alcohol, nicotine, and marijuana. The biological mechanisms by which these gateway drugs contribute to cocaine addiction are only beginning to be understood. We report that in the rat, prior alcohol consumption results in enhanced addiction-like behavior to cocaine, including continued cocaine use despite aversive consequences. Conversely, prior cocaine use has no effect on alcohol preference. Long-term, but not short-term, alcohol consumption promotes proteasome-mediated degradation of the nuclear histone deacetylases HDAC4 and HDAC5 in the nucleus accumbens, a brain region critical for reward-based memory...
November 2017: Science Advances
https://www.readbyqxmd.com/read/29074220/development-of-a-multiplexed-tumor-associated-autoantibody-based-blood-test-for-the-detection-of-colorectal-cancer
#20
Chung-Wei Fan, Yung-Bin Kuo, Geng-Pin Lin, Si-Min Chen, Shih-Hsien Chang, Bo-An Li, Err-Cheng Chan
BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide, and early diagnosis is vital to improving prognoses. We explored the diagnostic potential of a multiplex autoantibody panel as a biomarker for the detection of CRC by ELISA. METHODS: In total, 192 serum samples (92 CRC and 100 matched controls) were tested against a panel of 12 tumor-associated antigens (TAAs): RPH3AL, RPL36, SLP2, p53, survivin, ANAXA4, SEC61B, CCCAP, NYCO16, NMDAR, PLSCR1, and HDAC5...
October 23, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
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