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https://www.readbyqxmd.com/read/29784880/arginine-methylation-of-translocated-in-liposarcoma-tls-inhibits-its-binding-to-long-noncoding-rna-abrogating-tls-mediated-repression-of-cbp-p300-activity
#1
Wei Cui, Ryoma Yoneda, Naomi Ueda, Riki Kurokawa
Translocated in liposarcoma (TLS) is an RNA-binding protein and a transcription-regulatory sensor of DNA damage. TLS binds promoter-associated noncoding RNA (pncRNA) and inhibits histone acetyltransferase (HAT) activity of CREB-binding protein (CBP)/E1A-binding protein P300 (p300) on the cyclin D1 (CCND1) gene. Although post-translational modifications of TLS, such as arginine methylation, are known to regulate TLS's nucleocytoplasmic shuttling and assembly in stress granules, its interactions with RNAs remain poorly characterized...
May 21, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29784793/camp-inducible-coactivator-crtc3-attenuates-brown-adipose-tissue-thermogenesis
#2
Young-Sil Yoon, Wen-Wei Tsai, Sam Van de Velde, Zhijiang Chen, Kuo-Fen Lee, Donald A Morgan, Kamal Rahmouni, Shigenobu Matsumura, Ezra Wiater, Youngsup Song, Marc Montminy
In response to cold exposure, placental mammals maintain body temperature by increasing sympathetic nerve activity in brown adipose tissue (BAT). Triggering of β-adrenergic receptors on brown adipocytes stimulates thermogenesis via induction of the cAMP/PKA pathway. Although cAMP response element-binding protein (CREB) and its coactivators-the cAMP-regulated transcriptional coactivators (CRTCs)-mediate transcriptional effects of cAMP in most tissues, other transcription factors such as ATF2 appear critical for induction of thermogenic genes by cAMP in BAT...
May 21, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29783019/total-flavonoid-extract-of-epimedium-herb-increases-the-peak-bone-mass-of-young-rats-involving-enhanced-activation-of-the-ac10-camp-pka-creb-pathway
#3
Hui-Rong Xi, Hui-Ping Ma, Fang-Fang Yang, Yu-Hai Gao, Jian Zhou, Yuan-Yuan Wang, Wen-Yuan Li, Cory J Xian, Ke-Ming Chen
ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium sagittatum brevicornum Maxim. is an important traditional Chinese herb that has long been used to promote bone fracture healing and treat osteoporosis. AIM OF THE STUDY: Achieving peak bone mass by adolescence has now been accepted to be fundamental for preventing osteoporosis in adulthood life. This study investigated the possibility of increasing peak bone mass in young rats using the total flavonoid extract of Epimedium herb (TFE)...
May 18, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29778778/swimming-improves-cognitive-reserve-in-ovariectomized-rats-and-enhances-neuroprotection-after-global-cerebral-ischemia
#4
Meng Zhang, Yating Zhai, Yaping Sun, Wenli Zhang, Qian Li, Darrell Brann, Ruimin Wang
Cognitive reserve has been proposed to account for different responses to brain damage or pathology. Factors implicated to influence cognitive reserve include cognitive engagement, physical activity, leisure activities, stress levels, and diet. Furthermore, long-term ovariectomy (OVX), such as occurs in women that have underwent surgical menopause, has been reported to increase the risk of cognitive impairment. In the current study, we examined whether swimming improves cognitive function in long-term OVX-rats...
May 17, 2018: Brain Research
https://www.readbyqxmd.com/read/29777197/the-transition-state-structure-for-binding-between-taz1-of-cbp-and-the-disordered-hif-1%C3%AE-cad
#5
Ida Lindström, Eva Andersson, Jakob Dogan
Intrinsically disordered proteins (IDPs) are common in eukaryotes. However, relatively few experimental studies have addressed the nature of the rate-limiting transition state for the coupled binding and folding reactions involving IDPs. By using site-directed mutagenesis in combination with kinetics measurements we have here characterized the transition state for binding between the globular TAZ1 domain of CREB binding protein and the intrinsically disordered C-terminal activation domain of Hif-1α (Hif-1α CAD)...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29777135/n-methyl-d-aspartate-receptor-subtype-2b-antagonist-ro-25-6981-attenuates-neuropathic-pain-by-inhibiting-postsynaptic-density-95-expression
#6
Ling-Er Huang, Shao-Hui Guo, Lalita Thitiseranee, Yan Yang, Yan-Feng Zhou, Yong-Xing Yao
Postsynaptic density-95 (PSD-95) is a synaptic scaffolding protein that plays a crucial role in the development of neuropathic pain. However, the underlying mechanism remains unclear. To address the role of PSD-95 in N-methyl-D-aspartate receptor subtype 2B (NR2B) -mediated chronic pain, we investigated the relationship between PSD-95 activation and NR2B function in the spinal cord, by using a rat model of sciatic nerve chronic constriction injury (CCI). We demonstrate that the expression levels of total PSD-95 and cAMP response element binding protein (CREB), as well as phosphorylated NR2B, PSD-95, and CREB, in the spinal dorsal horn, and the interaction of NR2B with PSD-95 were increased in the CCI animals...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29775418/prolonged-activation-of-camp-signaling-leads-to-endothelial-barrier-disruption-via-transcriptional-repression-of-rras
#7
Carole Y Perrot, Junko Sawada, Masanobu Komatsu
The increase in cAMP levels in endothelial cells triggers cellular signaling to alter vascular permeability. It is generally considered that cAMP signaling stabilizes the endothelial barrier function and reduces permeability. However, previous studies have only examined the permeability shortly after cAMP elevation and thus have only investigated acute responses. Because cAMP is a key regulator of gene expression, elevated cAMP may have a delayed but profound impact on the endothelial permeability by altering the expression of the genes that are vital for the vessel wall stability...
May 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29772537/maternal-deprivation-promotes-hippocampal-neuronal-apoptosis-via-erk1-2-signaling
#8
Min Chen, Guoping He, Qiang Li
Neonatal maternal deprivation (MD) leads to depressive-like behaviors by promoting hippocampal neuronal apoptosis, but whether and how ERK1/2 signaling participates in MD-induced hippocampal neuronal apoptosis remains unclear. We therefore explored the role of ERK1/2 signaling pathway in neonatal MD-induced depression. Neonatal rats were divided into control group, PD group given intraperitoneal injections of MAPKK inhibitor (PD98059), MD group, and MD+PD group. The neonatal MD model was confirmed by behavioral tests...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29770701/mk2-mediates-macrophage-activation-and-acute-lung-injury-by-regulating-let-7e-mirna
#9
Yaxian Wu, Huiqiong He, Yunhe Ding, Sirui Liu, Depeng Zhang, Jun Wang, Hongchao Jiang, Dan Zhang, Lei Sun, Richard D Ye, Feng Qian
MAPK-activated protein kinase 2 (MK2) plays a critical role in the development of inflammation. However, the modulatory mechanisms in macrophage activation and acute lung injury (ALI) haven't been completely defined. Here, we reported that MK2 deficient mice (MK2-/-) protected against sepsis-induced ALI. In response to lipopolysaccharide (LPS) challenge, MK2-/- mice and myeloid cell-specific MK2 conditional knockout mice (MK2Lyz2-KO) exhibited attenuated inflammatory response, especially producing fewer amounts of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and macrophage inflammatory protein 2 (MIP-2)...
May 17, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29770155/neuroprotective-effect-and-molecular-mechanism-of-6-gingerol-against-scopolamine-induced-amnesia-in-c57bl-6-mice
#10
Chang-Yul Kim, Yongtaek Seo, Chan Lee, Gyu Hwan Park, Jung-Hee Jang
We have investigated the neuroprotective and memory enhancing effect of [6]-gingerol (GIN), a pungent ingredient of ginger, using an animal model of amnesia. To determine the neuroprotective effect of GIN on cognitive dysfunction, scopolamine (SCO, 1 mg/kg, i.p.) was injected into C57BL/6 mice, and a series of behavioral tests were conducted. SCO-induced behavior changes and memory impairments, such as decreased alteration (%) in Y-maze test, increased mean escape latency in water maze test, diminished step-through latency in passive avoidance test, and shortened freezing time in fear condition test, were significantly prevented and restored by the oral administration of GIN (10 or 25 mg/kg/day)...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29768201/activation-of-ephb2-forward-signaling-enhances-memory-consolidation
#11
Jessica M Alapin, Monica Dines, Maria Vassiliev, Tal Tamir, Alon Ram, Clifford Locke, Ji Yu, Raphael Lamprecht
EphB2 is involved in enhancing synaptic transmission and gene expression. To explore the roles of EphB2 in memory formation and enhancement, we used a photoactivatable EphB2 (optoEphB2) to activate EphB2 forward signaling in pyramidal neurons in lateral amygdala (LA). Photoactivation of optoEphB2 during fear conditioning, but not minutes afterward, enhanced long-term, but not short-term, auditory fear conditioning. Photoactivation of optoEphB2 during fear conditioning led to activation of the cAMP/Ca2+ responsive element binding (CREB) protein...
May 15, 2018: Cell Reports
https://www.readbyqxmd.com/read/29764237/neuroprotective-effect-of-clavulanic-acid-on-trimethyltin-tmt-induced-cytotoxicity-in-pc12-cells
#12
Samaneh Silakhori, Hossein Hosseinzadeh, Fatemeh Shaebani Behbahani, Soghra Mehri
Trimethyltin (TMT) is a short-chain trialkyltin with various applications in industry. In addition, it is a known neurotoxin, producing significant and selective neurodegeneration in the limbic system of both human and animals. Recently, effect of clavulanic acid (CA) in nervous system has been mentioned. Therefore, in this study, the role of CA in TMT-induced toxicity in PC12 cells was evaluated. For this study, PC12 cells were cultured and exposed to different concentrations of CA for 24 h. Then, TMT (20 µM) was added to cells...
May 15, 2018: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/29758466/structural-dynamics-and-quantum-mechanical-aspects-of-shikonin-derivatives-as-crebbp-bromodomain-inhibitors
#13
Sarmistha Mitra, Raju Dash
The Proteins involved in the chemical modification of lysine residues in histone, is currently being excessively focused as the therapeutic target for the treatment of cell related diseases like cancer. Among these proteins, the epigenetic reader, CREB-binding protein (CREBBP) bromodomain is one of the most prominent targets for effective anticancer drug design, which is responsible for the reorganization of acetylated histone lysine residues. Therefore, this study employed an integrative approach of structure based drug design, in combination with Molecular Dynamics (MD) and QM/MM study to identify as well as to describe the binding mechanism of two shikonin derivatives, acetylshikonin and propionylshikonin as inhibitors of CREBBP bromodomain...
May 4, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29757997/tetragonia-tetragonioides-pall-kuntze-regulates-androgen-production-in-a-letrozole-induced-polycystic-ovary-syndrome-model
#14
Bo-Jeong Pyun, Hyun Yang, Eunjin Sohn, Song Yi Yu, Dongoh Lee, Dong Ho Jung, Byoung Seob Ko, Hye Won Lee
Tetragonia tetragonioides (Pall.) Kuntze (TTK) is a medicinal plant traditionally used to treat various diseases such as diabetic, inflammatory, and female-related disorders. Polycystic ovary syndrome (PCOS) is a common endocrinological disorder in women of reproductive age, and hyperandrogenism is a prominent feature of PCOS resulting in anovulation and infertility. In this study, we investigated the effects of a TTK extract on androgen generation and regulation of steroidogenic enzymes in vitro and in vivo...
May 14, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29755318/arc-3-utr-splicing-leads-to-dual-and-antagonistic-effects-in-fine-tuning-arc-expression-upon-bdnf-signaling
#15
Chiara Paolantoni, Simona Ricciardi, Veronica De Paolis, Chinenye Okenwa, Caterina Catalanotto, Maria T Ciotti, Antonino Cattaneo, Carlo Cogoni, Corinna Giorgi
Activity-regulated cytoskeletal associated protein (Arc) is an immediate-early gene critically involved in synaptic plasticity and memory consolidation. Arc mRNA is rapidly induced by synaptic activation and a portion is locally translated in dendrites where it modulates synaptic strength. Being an activity-dependent effector of homeostatic balance, regulation of Arc is uniquely tuned to result in short-lived bursts of expression. Cis -Acting elements that control its transitory expression post-transcriptionally reside primarily in Arc mRNA 3' UTR...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29755294/inhibition-of-the-pi3k-but-not-the-mek-erk-pathway-sensitizes-human-glioma-cells-to-alkylating-drugs
#16
Bodo Haas, Veronika Klinger, Christina Keksel, Verena Bonigut, Daniela Kiefer, Julia Caspers, Julia Walther, Maria Wos-Maganga, Sandra Weickhardt, Gabriele Röhn, Marco Timmer, Roland Frötschl, Niels Eckstein
Background: Intrinsic chemoresistance of glioblastoma (GBM) is frequently owed to activation of the PI3K and MEK/ERK pathways. These signaling cascades are tightly interconnected however the quantitative contribution of both to intrinsic resistance is still not clear. Here, we aimed at determining the activation status of these pathways in human GBM biopsies and cells and investigating the quantitative impact of both pathways to chemoresistance. Methods: Receptor tyrosine kinase (RTK) pathways in temozolomide (TMZ) treatment naive or TMZ resistant human GBM biopsies and GBM cells were investigated by proteome profiling and immunoblotting of a subset of proteins...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29753890/characterization-of-the-promoter-of-white-spot-syndrome-virus-immediate-early-gene-wsv249
#17
Zi Yang, Xiaomin Xu, Fang Li, Feng Yang
White spot syndrome virus immediate early (IE) gene wsv249 encodes an E3 ubiquitin ligase that can interact with a shrimp ubiquitin-conjugating enzyme to mediate ubiquitination. In this study, to understand the transcriptional regulation of wsv249, a serial of 5'-truncated mutations were made on its promoter and the activities of mutated promoters was analyzed. Four 25 bp regions potentially containing either positive or negative regulatory elements were identified. Notably, the deletion of -275/-250, which abolished a cAMP-response element (CRE), greatly reduced the promoter activity by 84...
May 10, 2018: Virus Research
https://www.readbyqxmd.com/read/29753867/topiramate-mitigates-3-nitropropionic-acid-induced-striatal-neurotoxicity-via-modulation-of-ampa-receptors
#18
Heba N Shalaby, Dalia M El-Tanbouly, Hala F Zaki
Prevalence of glutamate receptor subunit 2 (GluR2)-lacking alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors is a hallmark of excitotoxicity-related neurodegenerative diseases. Topiramate (TPM) is a structurally novel anticonvulsant with a well-known modulatory effects on AMPA/kainate subtypes of glutamate receptors. The present study aimed at investigating the neuroprotective potential of TPM on 3-nitropropionic acid (3-NP)-induced striatal neurodegeneration and Huntington's disease-like symptoms...
May 10, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29753754/phosphatidylethanolamine-binding-protein-1-protects-ca1-neurons-against-ischemic-damage-via-erk-creb-signaling-in-mongolian-gerbils
#19
Hyo Young Jung, Su Bin Cho, Woosuk Kim, Dae Young Yoo, Moo-Ho Won, Goang-Min Choi, Tack-Geun Cho, Dae Won Kim, In Koo Hwang, Soo Young Choi, Seung Myung Moon
In the present study, we made a PEP-1-phosphatidylethanolamine-binding protein 1 (PEP-1-PEBP1) fusion protein to facilitate the transduction of PEBP1 into cells and observed significant ameliorative effects of PEP-1-PEBP1 against H2 O2 -induced neuronal damage and the formation of reactive oxygen species in the HT22 hippocampal cells. In addition, administration of PEP-1-PEBP1 fusion protein ameliorated H2 O2 -induced phosphorylation of extracellular signal-regulated kinases (ERK1/2) and facilitated the phosphorylation of cyclic-AMP response element binding protein (CREB) in HT22 cells after exposure to H2 O2 ...
May 10, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29751779/essential-role-of-atp6ap2-enrichment-in-caveolae-lipid-raft-microdomains-for-the-induction-of-neuronal-differentiation-of-stem-cells
#20
Nehman Makdissy, Katia Haddad, Jeanne D'arc AlBacha, Diana Chaker, Bassel Ismail, Albert Azar, Ghada Oreibi, David Ayoub, Ibrahim Achkar, Didier Quilliot, Ziad Fajloun
BACKGROUND: The subcellular distribution of prorenin receptor and adaptor protein ATP6AP2 may affect neurogenesis. In this study, we hypothesized that ATP6AP2 expression and subcellular relocalization from caveolae/lipid raft microdomains (CLR-Ms) to intracellular sites may correlate with neuronal differentiation (Neu-Dif) of adipose-derived mesenchymal stem cells (ADSCs). METHODS: Human ADSCs isolated from 24 healthy donors and 24 patients with neurological disorders (ND) were cultured and induced for Neu-Dif...
May 11, 2018: Stem Cell Research & Therapy
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