Read by QxMD icon Read


Marc N Wein, Yanke Liang, Olga Goransson, Thomas B Sundberg, Jinhua Wang, Elizabeth A Williams, Maureen J O'Meara, Nicolas Govea, Belinda Beqo, Shigeki Nishimori, Kenichi Nagano, Daniel J Brooks, Janaina S Martins, Braden Corbin, Anthony Anselmo, Ruslan Sadreyev, Joy Y Wu, Kei Sakamoto, Marc Foretz, Ramnik J Xavier, Roland Baron, Mary L Bouxsein, Thomas J Gardella, Paola Divieti-Pajevic, Nathanael S Gray, Henry M Kronenberg
Parathyroid hormone (PTH) activates receptors on osteocytes to orchestrate bone formation and resorption. Here we show that PTH inhibition of SOST (sclerostin), a WNT antagonist, requires HDAC4 and HDAC5, whereas PTH stimulation of RANKL, a stimulator of bone resorption, requires CRTC2. Salt inducible kinases (SIKs) control subcellular localization of HDAC4/5 and CRTC2. PTH regulates both HDAC4/5 and CRTC2 localization via phosphorylation and inhibition of SIK2. Like PTH, new small molecule SIK inhibitors cause decreased phosphorylation and increased nuclear translocation of HDAC4/5 and CRTC2...
October 19, 2016: Nature Communications
Jin Rong Ow, Monica Palanichamy Kala, Vinay Kumar Rao, Min Hee Choi, Narendra Bharathy, Reshma Taneja
In this study, we demonstrate that the lysine methyltransferase G9a inhibits sarcomere organization through regulation of the MEF2C-HDAC5 regulatory axis. Sarcomeres are essential for muscle contractile function. Presently, skeletal muscle disease and dysfunction at the sarcomere level has been associated with mutations of sarcomere proteins. This study provides evidence that G9a represses expression of several sarcomere genes and its over-expression disrupts sarcomere integrity of skeletal muscle cells. G9a inhibits MEF2C transcriptional activity that is essential for expression of sarcomere genes...
September 26, 2016: Scientific Reports
Hai-Yan Jia, Quan-Zhong Li, Li-Fang Lv
BACKGROUND/AIMS: Liver X receptor (LXR), a member of the nuclear receptor superfamily, is known to induce the expression of SREBP-1c and ChREBP, two master regulators of hepatic lipogenesis. Histone deacyetylases (HDACs) have been shown to play critical roles in glucose and lipids metabolism. However, the exact role of HDAC5 in lipogenesis remains elusive. METHODS: mRNA and protein levels of HDAC5 were analyzed by quantitative real-time PCR and Western blots in high-fat-diet-induced and leptin receptor deficiency-induced obese mice...
2016: Cellular Physiology and Biochemistry
Cheon Ho Park, Ju Hee Lee, Mi Young Lee, Jeong Hyun Lee, Byung Ho Lee, Kwang-Seok Oh
Urotensin II (UII) is a neural hormone that induces cardiac hypertrophy and may be involved in the pathogenesis of cardiac remodeling and heart failure. Hypertrophy has been linked to histone deacetylase 5 (HDAC5) phosphorylation and nuclear factor κB (NF-κB) translocation, both of which are predominantly mediated by G protein-coupled receptor kinase 5 (GRK5). In the present study, we found that UII rapidly and strongly stimulated nuclear export of HDAC5 and nuclear import of NF-κB in H9c2 cells overexpressing the urotensin II receptor (H9c2UT)...
November 2016: Molecular and Cellular Biochemistry
Johannes Fabian, Desirée Opitz, Kristina Althoff, Marco Lodrini, Barbara Hero, Ruth Volland, Anneleen Beckers, Katleen de Preter, Anneleen Decock, Nitin Patil, Mohammed Abba, Annette Kopp-Schneider, Kathy Astrahantseff, Jasmin Wünschel, Sebastian Pfeil, Maria Ercu, Annette Künkele, Jamie Hu, Theresa Thole, Leonille Schweizer, Gunhild Mechtersheimer, Daniel Carter, Belamy B Cheung, Odilia Popanda, Andreas V Deimling, Jan Koster, Rogier Versteeg, Manfred Schwab, Glenn M Marshall, Frank Speleman, Ulrike Erb, Margot Zoeller, Heike Allgayer, Thorsten Simon, Matthias Fischer, Andreas E Kulozik, Angelika Eggert, Olaf Witt, Johannes H Schulte, Hedwig E Deubzer
The systemic and resistant nature of metastatic neuroblastoma renders it largely incurable with current multimodal treatment. Clinical progression stems mainly from the increasing burden of metastatic colonization. Therapeutically inhibiting the migration-invasion-metastasis cascade would be of great benefit, but the mechanisms driving this cycle are as yet poorly understood. In-depth transcriptome analyses and ChIP-qPCR identified the cell surface glycoprotein, CD9, as a major downstream player and direct target of the recently described GRHL1 tumor suppressor...
August 27, 2016: Oncotarget
Everardus J van Zoelen, Isabel Duarte, José M Hendriks, Sebastian P van der Woning
BACKGROUND: Patients suffering from osteoporosis show an increased number of adipocytes in their bone marrow, concomitant with a reduction in the pool of human mesenchymal stem cells (hMSCs) that are able to differentiate into osteoblasts, thus leading to suppressed osteogenesis. METHODS: In order to be able to interfere with this process, we have investigated in-vitro culture conditions whereby adipogenic differentiation of hMSCs is impaired and osteogenic differentiation is promoted...
2016: Stem Cell Research & Therapy
Md Aminul Islam, Christine Große-Brinkhaus, Maren Julia Pröll, Muhammad Jasim Uddin, Sharmin Aqter Rony, Dawit Tesfaye, Ernst Tholen, Michael Hölker, Karl Schellander, Christiane Neuhoff
BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important viral diseases affecting swine industry worldwide. Despite routine farm vaccination, effective control strategies for PRRS remained elusive which underscores the need for in-depth studies to gain insight into the host immune response to vaccines. The current study aimed to investigate transcriptional responses to PRRS Virus (PRRSV) vaccine in the peripheral blood mononuclear cells (PBMCs) within 3 days following vaccination in German Landrace pigs...
2016: BMC Genomics
Shi-Ying Yuan, Jue Liu, Jun Zhou, Wei Lu, Hai-Yun Zhou, Li-Hong Long, Zhuang-Li Hu, Lan Ni, Yi Wang, Jian-Guo Chen, Fang Wang
Chronic stress induces altered energy metabolism and plays important roles in the etiology of depression, in which the glucocorticoid negative feedback is disrupted due to imbalanced glucocorticoid receptor (GR) functions. The mechanism underlying the dysregulation of GR by chronic stress remains elusive. In this study, we investigated the role of AMP-activated protein kinase (AMPK), the key enzyme regulating cellular energy metabolism, and related signaling pathways in chronic stress-induced GR dysregulation...
2016: PloS One
E Lee, S-Y Choi, B-H Bin, N-H Kim, K H Kim, D-H Choi, J Han, H Choi, A-Y Lee, T R Lee, E-G Cho
BACKGROUND: Cell migration plays a major role in the immune response and in tumorigenesis. Interferon-inducible T-cell alpha chemoattractant (ITAC) elicits a strong chemotactic response from immune cells. OBJECTIVES: To examine the effect of ITAC on the melanocytic migration and pigmentation and its involvement in the related disorders, and to investigate potential key players in these processes. METHODS: Human melanocytes or melanoma cells were treated with ITAC and migration assay was performed...
July 20, 2016: British Journal of Dermatology
Gyuhwi Lee, Jong Cheon Joo, Bo Yoon Choi, Anders M Lindroth, Soo Jung Park, Yoon Jung Park
BACKGROUND: The Paeonia lactiflora extract (PLE) has been reported to have neuroprotective effect against neurodegeneration that are induced by cellular stress such as oxidative stress. Its underlying mechanisms, however, remain unclear. In latest decades, emerging evidence has suggested that epigenetic mechanisms play a key role in gene regulation in response to the cellular stress. We investigated whether epigenetic modulation was involved in neuronal cell death by the neurotoxicant, 1-Methyl-4-phenylpyridinium (MPP(+)), and the neuroprotective effect of PLE...
2016: BMC Complementary and Alternative Medicine
Fumihiro Higuchi, Shusaku Uchida, Hirotaka Yamagata, Naoko Abe-Higuchi, Teruyuki Hobara, Kumiko Hara, Ayumi Kobayashi, Tatsushi Shintaku, Yukihiro Itoh, Takayoshi Suzuki, Yoshifumi Watanabe
: Chronic stress-induced aberrant gene expression in the brain and subsequent dysfunctional neuronal plasticity have been implicated in the etiology and pathophysiology of mood disorders. In this study, we examined whether altered expression of small, regulatory, noncoding microRNAs (miRNAs) contributes to the depression-like behaviors and aberrant neuronal plasticity associated with chronic stress. Mice exposed to chronic ultra-mild stress (CUMS) exhibited increased depression-like behaviors and reduced hippocampal expression of the brain-enriched miRNA-124 (miR-124)...
July 6, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Chang Peng, Xiaomei Luo, Qianlu Xing, Huichao Sun, Xupei Huang
Diastolic cardiac dysfunction can be caused by abnormality in cTnI expression during cardiogenesis. In this study, we investigated the effects of estrogen on the abnormal expression of cTnI in the hearts of neonatal mice and its potential epigenetic mechanisms. We then evaluated suberoylanilide hydroxamic acid (SAHA), a HDAC inhibitor, as a new target treatment of diastolic cardiac dysfunction. Postnatal day 0.5 C57BL/6 mice were injected with estrogen for 1 week, then the hearts of 7-day-old neonatal mice were retrieved for examination...
October 2016: Journal of Cellular Biochemistry
Denise Kemler, Oliver Dahley, Sven Roßwag, Margarethe Litfin, Olivier Kassel
The transcription factor Myocyte enhancer factor 2C (MEF2C) plays a key role in the late differentiation of skeletal muscle progenitor cells, the so-called myoblasts. During myoblast differentiation, both MEF2C expression and transcriptional activity are regulated. We have reported that nTRIP6, the nuclear isoform of the focal adhesion LIM domain protein TRIP6, acts as an adaptor transcriptional co-activator for several transcription factors. It interacts with the promoter-bound transcription factors and consequently mediates the recruitment of other co-activators...
2016: Scientific Reports
Antero Salminen, Kai Kaarniranta, Anu Kauppinen
The AMP-activated protein kinase (AMPK) and hypoxia-inducible factor (HIF) signaling pathways are evolutionarily-conserved survival mechanisms responding to two fundamental stresses, energy deficiency and/or oxygen deprivation. The AMPK and HIF pathways regulate the function of a survival network with several transcription factors, e.g. FOXO, NF-κB, NRF2, and p53, as well as with protein kinases and other factors, such as mTOR, ULK1, HDAC5, and SIRT1. Given that AMPK and HIF activation can enhance not only healthspan and lifespan but also cancer growth in a context-dependent manner; it seems that cancer cells can hijack certain survival factors to maintain their growth in harsh conditions...
August 2016: Biogerontology
Amanda J Guise, Ileana M Cristea
As a member of the class IIa family of histone deacetylases, the histone deacetylase 5 (HDAC5) is known to undergo nuclear-cytoplasmic shuttling and to be a critical transcriptional regulator. Its misregulation has been linked to prominent human diseases, including cardiac diseases and tumorigenesis. In this chapter, we describe several experimental methods that have proven effective for studying the functions and regulatory features of HDAC5. We present methods for assessing the subcellular localization, protein interactions, posttranslational modifications (PTMs), and activity of HDAC5 from the standpoint of investigating either the endogenous protein or tagged protein forms in human cells...
2016: Methods in Molecular Biology
Lin Li, Xiang-Jiao Yang
Histone deacetylases (HDACs) regulate various nuclear and cytoplasmic processes. In mammals, these enzymes are divided into four classes, with class II further divided into two subclasses: IIa (HDAC4, HDAC5, HDAC7, HDAC9) and IIb (HDAC6 and HDAC10). While HDAC6 is mainly cytoplasmic and HDAC10 is pancellular, class IIa HDACs are dynamically shuttled between the nucleus and cytoplasm in a signal-dependent manner, indicating that they are unique signal transducers able to transduce signals from the cytoplasm to chromatin in the nucleus...
2016: Methods in Molecular Biology
C Cao, S N Vasilatos, R Bhargava, J L Fine, S Oesterreich, N E Davidson, Y Huang
We have previously demonstrated that crosstalk between lysine-specific demethylase 1 (LSD1) and histone deacetylases (HDACs) facilitates breast cancer proliferation. However, the underlying mechanisms are largely unknown. Here, we report that expression of HDAC5 and LSD1 proteins were positively correlated in human breast cancer cell lines and tissue specimens of primary breast tumors. Protein expression of HDAC5 and LSD1 was significantly increased in primary breast cancer specimens in comparison with matched-normal adjacent tissues...
May 23, 2016: Oncogene
Anqi Li, Zebing Liu, Ming Li, Shuling Zhou, Yan Xu, Yaoxing Xiao, Wentao Yang
PURPOSE: Histone deacetylase 5 (HDAC5) is an important protein in neural and cardiac diseases and a potential drug target. However, little is known regarding the specific role of HDAC5 in breast cancer (BC). We aimed to evaluate HDAC5 expression in human breast tumors and to determine the effects of the inhibition of HDAC5 expression in BC cells. EXPERIMENTAL DESIGN: HDAC5 expression was evaluated in BC patients and was correlated with clinical features and with patient prognosis...
May 10, 2016: Oncotarget
Zarko V Boskovic, Melissa M Kemp, Allyson M Freedy, Vasanthi S Viswanathan, Marius S Pop, Jason H Fuller, Nicole M Martinez, Samuel O Figueroa Lazú, Jiyoung A Hong, Timothy A Lewis, Daniel Calarese, James D Love, Amedeo Vetere, Steven C Almo, Stuart L Schreiber, Angela N Koehler
Unbiased binding assays involving small-molecule microarrays were used to identify compounds that display unique patterns of selectivity among members of the zinc-dependent histone deacetylase family of enzymes. A novel, hydroxyquinoline-containing compound, BRD4354, was shown to preferentially inhibit activity of HDAC5 and HDAC9 in vitro. Inhibition of deacetylase activity appears to be time-dependent and reversible. Mechanistic studies suggest that the compound undergoes zinc-catalyzed decomposition to an ortho-quinone methide, which covalently modifies nucleophilic cysteines within the proteins...
July 15, 2016: ACS Chemical Biology
Christopher J Clarke, Achraf A Shamseddine, Joseph J Jacob, Gabrielle Khalife, Tara A Burns, Yusuf A Hannun
Neutral sphingomyelinase-2 (nSMase2) is a key ceramide-producing enzyme in cellular stress responses. While many posttranslational regulators of nSMase2 are known, emerging evidence suggests a more protracted regulation of nSMase2 at the transcriptional level. Previously, we reported that nSMase2 is induced by all-trans retinoic acid (ATRA) in MCF7 cells and implicated nSMase2 in ATRA-induced growth arrest. Here, we further investigated how ATRA regulates nSMase2. We find that ATRA regulates nSMase2 transcriptionally through the retinoic acid receptor-α, but this is independent of previously identified transcriptional regulators of nSMase2 (Sp1, Sp3, Runx2) and is not through increased promoter activity...
May 2016: Journal of Lipid Research
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"