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https://www.readbyqxmd.com/read/29325547/paracrine-and-epigenetic-control-of-caf-induced-metastasis-the-role-of-hotair-stimulated-by-tgf-%C3%A3-1-secretion
#1
Yu Ren, Huan-Huan Jia, Yi-Qi Xu, Xuan Zhou, Xiao-Hui Zhao, Yun-Fei Wang, Xin Song, Zhi-Yan Zhu, Ting Sun, Yan Dou, Wei-Ping Tian, Xiu-Lan Zhao, Chun-Sheng Kang, Mei Mei
BACKGROUND: The communication between carcinoma associated fibroblasts (CAFs) and cancer cells facilitate tumor metastasis. In this study, we further underlying the epigenetic mechanisms of CAFs feed the cancer cells and the molecular mediators involved in these processes. METHODS: MCF-7 and MDA-MB-231 cells were treated with CAFs culture conditioned medium, respectively. Cytokine antibody array, enzyme-linked immunosorbent assay, western blotting and immunofluorescence were used to identify the key chemokines...
January 11, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29314417/a-nestin-cdk5-drp1-axis-regulates-neural-stem-progenitor-cell-stemness-via-a-metabolic-shift
#2
Jiancheng Wang, Yinong Huang, Jianye Cai, Qiong Ke, Jiaqi Xiao, Weijun Huang, Hongyu Li, Yuan Qiu, Yi Wang, Bin Zhang, Haoxiang Wu, Yanan Zhang, Xin Sui, Adham Sameer A Bardeesi, Andy Peng Xiang
Neural stem/progenitor cells (NSPCs) transplantation provides an alternative approach for various central nervous system (CNS) diseases treatment, while the difficulties in NSPC acquisition and expansion limit their further application. Unveiling the mechanism of NSPC stemness regulation may contribute to its further application. Nestin, generally recognized as a marker of NSPCs, plays a crucial role in the CNS development and NSPC stemness maintenance. Here, we report that Nestin loss triggers mitochondrial network remodeling and enhances oxidative phosphorylation (OXPHOS) in NSPCs treated with Nestin RNA interference (RNAi)...
January 3, 2018: Stem Cells
https://www.readbyqxmd.com/read/29312535/clinical-role-and-biological-function-of-cdk5-in-hepatocellular-carcinoma-a-study-based-on-immunohistochemistry-rna-seq-and-in-vitro-investigation
#3
Rui Zhang, Peng Lin, Hong Yang, Yun He, Yi-Wu Dang, Zhen-Bo Feng, Gang Chen
To investigate the clinical role and biological function of cyclin-dependent kinase 5 (CDK5) in hepatocellular carcinoma (HCC), 412 surgically resected tissue samples (HCC, n=171; non-HCC=241) were obtained and analyzed with immunohistochemistry. The diagnostic and prognostic values of CDK5 expression levels in HCC were clarified. Moreover, RNA-seq data or microarray datasets from The Cancer Genome Atlas (TCGA) (HCC, n=374; normal, n=50) or other public databases (HCC, n=1864; non-tumor=1995) regarding CDK5 in HCC were extracted and examined...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29311579/structural-basis-for-the-enhanced-anti-diabetic-efficacy-of-lobeglitazone-on-ppar%C3%AE
#4
Jun Young Jang, Hwan Bae, Yong Jae Lee, Young Il Choi, Hyun-Jung Kim, Seung Bum Park, Se Won Suh, Sang Wan Kim, Byung Woo Han
Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily. It functions as a ligand-activated transcription factor and plays important roles in the regulation of adipocyte differentiation, insulin resistance, and inflammation. Here, we report the crystal structures of PPARγ in complex with lobeglitazone, a novel PPARγ agonist, and with rosiglitazone for comparison. The thiazolidinedione (TZD) moiety of lobeglitazone occupies the canonical ligand-binding pocket near the activation function-2 (AF-2) helix (i...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29308980/modulation-of-trpa1-channel-activity-by-cdk5-in-sensory-neurons
#5
Michael A Sulak, Monica Ghosh, Pritam Sinharoy, Spencer R Andrei, Derek S Damron
Transient receptor potential cation channel, subfamily A, member 1 (TRPA1), is activated by a broad range of noxious stimuli. Cdk5, a member of the Cdk family, has recently been identified as a modulator of pain signaling pathways. In the current study, we investigated the extent to which Cdk5 modulates TRPA1 activity. Cdk5 inhibition was found to attenuate TRPA1 response to agonist in mouse DRG sensory neurons. Additionally, the presence of active Cdk5 was associated with increased TRPA1 phosphorylation in transfected HEK293 cells that was roscovitine-sensitive and absent in the mouse mutant S449A full-length channel...
January 8, 2018: Channels
https://www.readbyqxmd.com/read/29307714/the-novel-brassinosteroid-analog-br4848-inhibits-angiogenesis-in-human-endothelial-cells-and-induces-apoptosis-in-human-cancer-cells-in-vitro
#6
Lucie Rárová, David Sedlák, Jana Oklestkova, Jana Steigerová, Johanna Liebl, Stefan Zahler, Petr Bartůněk, Zdeněk Kolář, Ladislav Kohout, Miroslav Kvasnica, Miroslav Strnad
We report the synthesis and detailed biological study of the synthetic brassinosteroid analog 2α,3α-dihydroxy-6-oxo-5α-androstan-17β-yl N-(tert-butoxycarbonyl)-D,L-valinate (BR4848). The panel of cancer cell lines was used for characterization of its antiproliferative activity, yet had no adverse effects in normal human fibroblasts. In HeLa cells, BR4848-induced apoptosis was accompanied by increase of apoptotic subG1 cells, PARP-1 and caspase-7 fragmentation, downregulation of Bcl-2 and Mcl-1, an increase in caspase activity and G2/M phase cell cycle arrest...
January 4, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29301548/inhibition-of-cyclin-dependent-kinase-5-affects-early-neuroinflammatory-signalling-in-murine-model-of-amyloid-beta-toxicity
#7
Anna Wilkaniec, Magdalena Gąssowska-Dobrowolska, Marcin Strawski, Agata Adamczyk, Grzegorz A Czapski
BACKGROUND: Cyclin-dependent kinase 5 (Cdk5) belongs to the family of proline-directed serine/threonine kinases and plays a critical role in neuronal differentiation, migration, synaptogenesis, plasticity, neurotransmission and apoptosis. The deregulation of Cdk5 activity was observed in post mortem analysis of brain tissue of Alzheimer's disease (AD) patients, suggesting the involvement of Cdk5 in the pathomechanism of this neurodegenerative disease. However, our recent study demonstrated the important function of Cdk5 in regulating inflammatory reaction...
January 4, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29291439/novel-non-sulfonamide-5-ht6-receptor-partial-inverse-agonist-in-a-group-of-imidazo-4-5-b-pyridines-with-cognition-enhancing-properties
#8
David Vanda, Miroslav Soural, Vittorio Canale, Séverine Chaumont-Dubel, Grzegorz Satała, Tomasz Kos, Petr Funk, Veronika Fülöpová, Barbora Lemrová, Paulina Koczurkiewicz, Elżbieta Pękala, Andrzej J Bojarski, Piotr Popik, Philippe Marin, Paweł Zajdel
A small library of novel 3H-imidazo[4,5-b]pyridine and 1H-imidazo[4,5-c]pyridine derivatives was designed and synthesized as non-sulfonamide 5-HT6 receptor ligands. In vitro evaluation allowed to identify compound 17 (2-ethyl-3-(3-fluorobenzyl)-7-(piperazin-1-yl)-3H-imidazo[4,5-b]pyridine) as potent 5-HT6 receptor partial inverse agonist in Gs signaling (Ki = 6 nM, IC50 = 17.6 nM). Compound 17 displayed high metabolic stability, favorable cytochrome P450 isoenzyme (2D6, 3A4) profile, did not affect PgP-protein binding, without evoking mutagenic effects...
December 16, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29288339/cdk5-contributes-to-huntington-s-disease-learning-and-memory-deficits-via-modulation-of-brain-region-specific-substrates
#9
Elena Alvarez-Periel, Mar Puigdellívol, Verónica Brito, Florian Plattner, James A Bibb, Jordi Alberch, Silvia Ginés
Cognitive deficits are a major hallmark of Huntington's disease (HD) with a great impact on the quality of patient's life. Gaining a better understanding of the molecular mechanisms underlying learning and memory impairments in HD is, therefore, of critical importance. Cdk5 is a proline-directed Ser/Thr kinase involved in the regulation of synaptic plasticity and memory processes that has been associated with several neurodegenerative disorders. In this study, we aim to investigate the role of Cdk5 in learning and memory impairments in HD using a novel animal model that expresses mutant huntingtin (mHtt) and has genetically reduced Cdk5 levels...
December 29, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29234273/indirubin-derivative-7-bromoindirubin-3-oxime-7bio-attenuates-a%C3%AE-oligomer-induced-cognitive-impairments-in-mice
#10
Liping Chen, Chunhui Huang, Jieyi Shentu, Minjun Wang, Sicheng Yan, Fei Zhou, Zaijun Zhang, Chuang Wang, Yifan Han, Qinwen Wang, Wei Cui
Indirubins are natural occurring alkaloids extracted from indigo dye-containing plants. Indirubins could inhibit various kinases, and might be used to treat chronic myelocytic leukemia, cancer and neurodegenerative disorders. 7-bromoindirubin-3-oxime (7Bio), an indirubin derivative derived from indirubin-3-oxime, possesses inhibitory effects against cyclin-dependent kinase-5 (CDK5) and glycogen synthase kinase-3β (GSK3β), two pharmacological targets of Alzheimer's disease (AD). In this study, we have discovered that 2...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29227343/golgi-fragmentation-induced-by-overactivated-cyclin-dependent-kinase-5-is-associated-with-isoflurane-induced-neurotoxicity
#11
Fang-Fang Miao, Cui-Cui Kong, Yan Wu, Long Fan, Tian-Long Wang
Overactivated cyclin-dependent kinase 5 (Cdk5) induces Golgi fragmentation, which interrupts the processing and trafficking of secretory cargo and subsequently synaptic plasticity and synaptogenesis, and even leads to neuronal cell death. Cdk5 overactivation and subsequent Golgi fragmentation are involved in many neurodegenerative diseases. However, whether isoflurane-induced neurotoxicity is relevant to aberrant Cdk5 activation and subsequent Golgi fragmentation remains unknown. In the present study, we explored the underlying molecular mechanisms of isoflurane-induced neurotoxicity in primary cultured hippocampal neurons...
December 8, 2017: Neuroreport
https://www.readbyqxmd.com/read/29227247/stress-induced-cdk5-activity-enhances-cytoprotective-basal-autophagy-in-drosophila-melanogaster-by-phosphorylating-acinus-at-serine437
#12
Nilay Nandi, Lauren K Tyra, Drew Stenesen, Helmut Krämer
Cdk5 is a post-mitotic kinase with complex roles in maintaining neuronal health. The various mechanisms by which Cdk5 inhibits and promotes neurodegeneration are still poorly understood. Here, we show that in Drosophila melanogaster Cdk5 regulates basal autophagy, a key mechanism suppressing neurodegeneration. In a targeted screen, Cdk5 genetically interacted with Acinus (Acn), a primarily nuclear protein, which promotes starvation-independent, basal autophagy. Loss of Cdk5, or its required cofactor p35, reduces S437-Acn phosphorylation, whereas Cdk5 gain-of-function increases pS437-Acn levels...
December 11, 2017: ELife
https://www.readbyqxmd.com/read/29225566/cdk5-is-essential-for-amphetamine-to-increase-dendritic-spine-density-in-hippocampal-pyramidal-neurons
#13
Soledad Ferreras, Guillermo Fernández, Víctor Danelon, María V Pisano, Luján Masseroni, Christopher A Chapleau, Favio A Krapacher, Estela C Mlewski, Daniel H Mascó, Carlos Arias, Lucas Pozzo-Miller, María G Paglini
Psychostimulant drugs of abuse increase dendritic spine density in reward centers of the brain. However, little is known about their effects in the hippocampus, where activity-dependent changes in the density of dendritic spine are associated with learning and memory. Recent reports suggest that Cdk5 plays an important role in drug addiction, but its role in psychostimulant's effects on dendritic spines in hippocampus remain unknown. We used in vivo and in vitro approaches to demonstrate that amphetamine increases dendritic spine density in pyramidal neurons of the hippocampus...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29209207/antiepileptic-and-neuroprotective-effects-of-oleamide-in-rat-striatum-on-kainate-induced-behavioral-seizure-and-excitotoxic-damage-via-calpain-inhibition
#14
Hye Yeon Nam, Eun Jung Na, Eunyoung Lee, Youngjoo Kwon, Hwa-Jung Kim
Oleamide was first known as a sleep-inducing fatty acid amide, and later shown to have wide range of neuropharmacological effects upon different neurochemical systems. However, the effects of oleamide on brain damage have scarcely been studied, and the molecular mechanisms and sites of its action remain elusive. Kainic acid (KA) has been used to produce an epileptic animal model that mimics human temporal lobe epilepsy and to induce calpain-activated excitotoxicity, which occurs in numerous neurodegenerative disorders...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29207020/quercetin-inhibits-okadaic-acid-induced-tau-protein-hyperphosphorylation-through-the-ca2-%C3%A2-calpain%C3%A2-p25%C3%A2-cdk5-pathway-in-ht22-cells
#15
Xiu-Yin Shen, Tao Luo, Sheng Li, Ou-Yang Ting, Feng He, Jie Xu, Hua-Qiao Wang
Alzheimer's disease (AD) is a common neurodegenerative disorder characterized by aberrant tau protein hyperphosphorylation, which eventually leads to the formation of neurofibrillary tangles. Hyperphosphorylated tau protein is considered as a vital factor in the development of AD and is highly associated with cognitive impairment. Therefore, it is recognized to be a potential therapeutic target. Quercetin (QUE) is a naturally occurring flavonoid compound. In the present study, the inhibitory effect of QUE on okadaic acid (OA)-induced tau protein hyperphosphorylation in HT22 cells was explored...
November 22, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29196663/a-ser75-to-asp-phospho-mimicking-mutation-in-src-accelerates-ageing-related-loss-of-retinal-ganglion-cells-in-mice
#16
Kenji Kashiwagi, Sadahiro Ito, Shuichiro Maeda, Goro Kato
Src knockout mice show no detectable abnormalities in central nervous system (CNS) post-mitotic neurons, likely reflecting functional compensation by other Src family kinases. Cdk1- or Cdk5-dependent Ser75 phosphorylation in the amino-terminal Unique domain of Src, which shares no homology with other Src family kinases, regulates the stability of active Src. To clarify the roles of Src Ser75 phosphorylation in CNS neurons, we established two types of mutant mice with mutations in Src: phospho-mimicking Ser75Asp (SD) and non-phosphorylatable Ser75Ala (SA)...
December 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29158185/cdk5-mediated-phosphorylation-of-sirt2-contributes-to-depressive-like-behavior-induced-by-social-defeat-stress
#17
Zheng Zhang, Pei Zhang, Guang-Jian Qi, Feng-Juan Jiao, Qing-Zhi Wang, Jian-Guo Yan, Feng He, Qian Zhang, Ze-Xi Lv, Xiang Peng, Hong-Wei Cai, Xiaoqian Chen, Ning Sun, Bo Tian
Major depressive disorder (MDD) is a common, severe and recurrent psychiatric disorder worldwide; however, the underlying neuropathological mechanisms remain elusive. Histone deacetylases (HDACs) appear to play an essential role in depression. As the class III HDACs, Sirt1 and Sirt2 have attracted the most interest in the nervous system. Indeed, chronic stress decreased Sirt1 activity and down-regulated Sirt1 gene expression in MDD. Nevertheless, there is a paucity of literature on the role of Sirt2. To study the role of Sirt2 we established a MDD mouse model in wild type and Sirt2 knockout C57BL/6 mice using social defeat stress (SDS)...
November 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29154274/cognitive-decline-in-preclinical-alzheimer-s-disease-amyloid-beta-versus-tauopathy
#18
Colin M Huber, Connor Yee, Taylor May, Apoorva Dhanala, Cassie S Mitchell
 We perform a large-scale meta-analysis of 51 peer-reviewed 3xTg-AD mouse publications to compare Alzheimer's disease (AD) quantitative clinical outcome measures, including amyloid-β (Aβ), total tau, and phosphorylated tau (pTau), with cognitive performance in Morris water maze (MWM) and Novel Object Recognition (NOR). "High" levels of Aβ (Aβ40, Aβ42) showed significant but weak trends with cognitive decline (MWM: slope = 0.336, R2 = 0.149, n = 259, p < 0.001; NOR: slope = 0.156, R2 = 0...
November 14, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29152905/the-gait-translational-control-system
#19
REVIEW
Abul Arif, Peng Yao, Fulvia Terenzi, Jie Jia, Partho Sarothi Ray, Paul L Fox
The interferon (IFN)-γ-activated inhibitor of translation (GAIT) system directs transcript-selective translational control of functionally related genes. In myeloid cells, IFN-γ induces formation of a multiprotein GAIT complex that binds structural GAIT elements in the 3'-untranslated regions (UTRs) of multiple inflammation-related mRNAs, including ceruloplasmin and VEGF-A, and represses their translation. The human GAIT complex is a heterotetramer containing glutamyl-prolyl tRNA synthetase (EPRS), NS1-associated protein 1 (NSAP1), ribosomal protein L13a (L13a), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH)...
November 20, 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/29150675/mechanisms-by-which-in-vitro-meiotic-arrest-and-sexual-maturity-improve-developmental-potential-of-mouse-oocytes
#20
Fei Chen, Juan Lin, Xue Sun, Bin Xiao, Shu-Fen Ning, Shuai Zhu, Hui-Li Wang, Jing-He Tan
To study the relationship between chromatin condensation, gene transcription and developmental competence during oocyte maturation and to explore the mechanisms by which meiotic arrest maintenance (MAM) and sexual maturity improve oocyte competence, we examined effects of MAM with roscovitine or db-cAMP on chromatin condensation, gene transcription and developmental potential of NSN or SN oocytes from prepubertal or adult mice. MAM with roscovitine improved the developmental competence and global gene transcription of prepubertal NSN (prep-NSN) and adult-SN oocytes while having no effect on those of prep-SN oocytes...
November 17, 2017: Scientific Reports
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