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https://www.readbyqxmd.com/read/28327597/molecular-signaling-underlying-bulleyaconitine-a-baa-induced-microglial-expression-of-prodynorphin
#1
Teng-Fei Li, Hai-Yun Wu, Yi-Rui Wang, Xin-Yan Li, Yong-Xiang Wang
Bulleyaconitine (BAA) has been shown to possess antinociceptive activities by stimulation of dynorphin A release from spinal microglia. This study investigated its underlying signal transduction mechanisms. The data showed that (1) BAA treatment induced phosphorylation of CREB (rather than NF-κB) and prodynorphin expression in cultured primary microglia, and antiallodynia in neuropathy, which were totally inhibited by the CREB inhibitor KG-501; (2) BAA upregulated phosphorylation of p38 (but not ERK or JNK), and the p38 inhibitor SB203580 (but not ERK or JNK inhibitor) and p38β gene silencer siRNA/p38β (but not siRNA/p38α) completely blocked BAA-induced p38 phosphorylation and/or prodynorphin expression, and antiallodynia; (3) BAA stimulated cAMP production and PKA phosphorylation, and the adenylate cyclase inhibitor DDA and PKA inhibitor H-89 entirely antagonized BAA-induced prodynorphin expression and antiallodynia; (4) The Gs-protein inhibitor NF449 completely inhibited BAA-increased cAMP level, prodynorphin expression and antiallodynia, whereas the antagonists of noradrenergic, corticotrophin-releasing factor, A1 adenosine, formyl peptide, D1/D2 dopamine, and glucagon like-peptide-1 receptors failed to block BAA-induced antiallodynia...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327356/type-2-inositol-trisphosphate-receptor-gene-expression-in-hepatocytes-is-regulated-by-cyclic-amp
#2
Emma Kruglov, M Ananthanarayanan, Pedro Sousa, Jittima Weerachayaphorn, Mateus T Guerra, Michael H Nathanson
The type 2 inositol 1,4,5-trisphosphate receptor (IP3R2) is the principal intracellular Ca(2+) release channel in hepatocytes, and so is important for bile secretion and other functions. IP3R2 activity is regulated in part by post-translational modifications but little is known about transcriptional regulation of its expression. We found that both IP3R2 mRNA and protein levels in liver were increased during fasting. Treatment of hepatocytes with forskolin or 8-CPT-cAMP also increased IP3R2, and this was reduced by actinomycin D...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28326743/dopamine-receptors-modulate-t-lymphocytes-via-inhibition-of-camp-creb-signaling-pathway
#3
(no author information available yet)
OBJECTIVES: We have previously reported that dopamine D2-like receptors including D2, D3 and D4 receptors are more important in mediating modulation of T cells than dopamine D1-like receptors (D1 and D5 receptors). Here we aimed to clarify the role of D2-like receptors in regulation of differentiation and function of T lymphocyte subsets, including helper T (Th)1, Th2, Th17 and regulatory T (Treg) cells. METHODS: Lymphocytes, separated from the mesenteric lymph nodes of mice, were stimulated with concanavalin A (Con A) and treated with the D2-like receptor agonist quinpirole or the antagonist haloperidol...
December 22, 2016: Neuro Endocrinology Letters
https://www.readbyqxmd.com/read/28323246/the-role-of-spinal-gabab-receptors-in-cancelr-induced-bone-pain-in-rats
#4
Ya-Qun Zhou, Shu-Ping Chen, Dai-Qiang Liu, Anne Manyande, Wen Zhang, Shao-Bing Yang, Bing-Rui Xiong, Qiao-Chu Fu, Zhen-Peng Song, Heike Rittner, Da-Wei Ye, Yu-Ke Tian
Cancer-induced bone pain (CIBP) remains a major challenge in advanced cancer patients due to our lack of understanding of its mechanisms. Previous studies have demonstrated the vital role of GABAB receptors (GABABRs) in regulating nociception and various neuropathic pain models have shown diminished activity of GABABRs. However, the role of spinal GABABRs in CIBP remains largely unknown. In this study, we investigated the specific cellular mechanisms of GABABRs in the development and maintenance of CIBP in rats...
March 18, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28322447/regulation-role-of-crtc3-in-skeletal-muscle-and-adipose-tissue
#5
REVIEW
Jiaqi Liu, Ziye Xu, Weiche Wu, Yizhen Wang, Tizhong Shan
The cyclic adenosine monophosphate (cAMP) - protein kinase A (PKA) signaling pathway plays important role in regulating energy homeostasis. Many of the effects of the cAMP-PKA signaling is mediated through the cAMP responsive element binding protein (CREB) and its coactivator CREB-regulated transcription coactivators (CRTCs). CRTC3 is a member of CRTCs family proteins and plays important roles in glucose and energy metabolism. Previous studies shown that global knockout of CRTC3 enhances oxygen consumption and energy expenditure and subsequently protects the knockout animal against obesity...
March 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28322281/identification-of-a-novel-fast-acting-gabaergic-antidepressant
#6
K M J McMurray, M J Ramaker, A M Barkley-Levenson, P S Sidhu, P K Elkin, M K Reddy, M L Guthrie, J M Cook, V H Rawal, L A Arnold, S C Dulawa, A A Palmer
Current pharmacotherapies for depression exhibit slow onset, side effects and limited efficacy. Therefore, identification of novel fast-onset antidepressants is desirable. GLO1 is a ubiquitous cellular enzyme responsible for the detoxification of the glycolytic byproduct methylglyoxal (MG). We have previously shown that MG is a competitive partial agonist at GABA-A receptors. We examined the effects of genetic and pharmacological inhibition of GLO1 in two antidepressant assay models: the tail suspension test (TST) and the forced swim test (FST)...
March 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28321769/n-propargyl-caffeamide-paca-ameliorates-dopaminergic-neuronal-loss-and-motor-dysfunctions-in-mptp-mouse-model-of-parkinson-s-disease-and-in-mpp-induced-neurons-via-promoting-the-conversion-of-prongf-to-ngf
#7
Dan Luo, Jia Zhao, Yuanyuan Cheng, Simon Ming-Yuen Lee, Jianhui Rong
Insufficient production of nerve growth factor (NGF) is implicated in Parkinson's disease (PD). We recently discovered that caffeic acid derivative N-propargyl caffeamide (PACA) not only potentiated NGF-induced neurite outgrowth but also attenuated 6-hydroxydopamine neurotoxicity in neuronal culture. The aim of the present study was to investigate whether PACA could increase NGF levels against 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) neurotoxicity in a mouse PD model. We induced parkinsonism in mice by intraperitoneal injection of MPTP for seven consecutive days...
March 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28321434/transient-creb-mediated-transcription-is-key-in-direct-neuronal-reprogramming
#8
Sergio Gascón, Felipe Ortega, Magdalena Götz
Combinations of neuronal determinants and/or small-molecules such as Forskolin (Fk) can be used to convert different cell types into neurons. As Fk is known to activate cAMP-dependent pathways including CREB-activity, we aimed here to determine the role of CREB in reprogramming - including its temporal profile. We show that transient expression of the dominant-positive CREB-VP16 followed by its inactivation mediated by the dominant-negative ICER improves neuronal conversion of astrocytes mediated by the neurogenic determinant Ascl1...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28319198/methamphetamine-induces-shati-nat8l-expression-in-the-mouse-nucleus-accumbens-via-creb-and-dopamine-d1-receptor-dependent-mechanism
#9
Kyosuke Uno, Toh Miyazaki, Kengo Sodeyama, Yoshiaki Miyamoto, Atsumi Nitta
Shati/Nat8L significantly increased in the nucleus accumbens (NAc) of mice after repeated methamphetamine (METH) treatment. We reported that Shati/Nat8L overexpression in mouse NAc attenuated METH-induced hyperlocomotion, locomotor sensitization, and conditioned place preference. We recently found that Shati/Nat8L overexpression in NAc regulates the dopaminergic neuronal system via the activation of group II mGluRs by elevated N-acetylaspartylglutamate following N-acetylaspartate increase due to the overexpression...
2017: PloS One
https://www.readbyqxmd.com/read/28315455/7-8-dihydroxyflavone-facilitates-the-action-exercise-to-restore-plasticity-and-functionality-implications-for-early-brain-trauma-recovery
#10
Gokul Krishna, Rahul Agrawal, Yumei Zhuang, Zhe Ying, Afshin Paydar, Neil G Harris, Luiz Fernando F Royes, Fernando Gomez-Pinilla
Metabolic dysfunction accompanying traumatic brain injury (TBI) severely impairs the ability of injured neurons to comply with functional demands. This limits the success of rehabilitative strategies by compromising brain plasticity and function, and highlights the need for early interventions to promote energy homeostasis. We sought to examine whether the TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF) normalizes brain energy deficits and restablishes more normal patterns of functional connectivity, while enhancing the effects of exercise during post-TBI period...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28314773/glucocorticoid-receptor-signaling-represses-the-antioxidant-response-by-inhibiting-histone-acetylation-mediated-by-the-transcriptional-activator-nrf2
#11
Md Morshedul Alam, Keito Okazaki, Linh Thi Thao Nguyen, Nao Ota, Hiroshi Kitamura, Shohei Murakami, Hiroki Shima, Kazuhiko Igarashi, Hiroki Sekine, Hozumi Motohashi
NRF2 (nuclear factor erythroid 2-related factor 2) is a key transcriptional activator that mediates the inducible expression of antioxidant genes. NRF2 is normally ubiquitinated by KEAP1 (Kelch-like ECH-associated protein 1) and subsequently degraded by proteasomes. Inactivation of KEAP1 by oxidative stress or electrophilic chemicals allows NRF2 to activate transcription through binding to antioxidant response elements (AREs) and recruiting histone acetyltransferase CBP (CREB-binding protein). While KEAP1-dependent regulation is a major determinant of NRF2 activity, NRF2-mediated transcriptional activation varies from context to context, suggesting other intracellular signaling cascades may impact NRF2 function...
March 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28302794/dna-sequence-dependent-epigenetic-inheritance-of-gene-silencing-and-histone-h3k9-methylation
#12
Xiaoyi Wang, Danesh Moazed
Epigenetic inheritance mechanisms play fundamental roles in maintaining cellular memory of gene expression states. In fission yeast, histone H3 lysine 9 (H3K9me) is methylated at heterochromatic domains. These domains can be epigenetically inherited when epi1+, encoding an enzyme that promotes H3K9 demethylation, is deleted. How native epigenetic states are stably maintained in epe1(+) cells remains unknown. Here, we developed a system to examine the role of DNA sequence and genomic context in propagation of a cis-heritable H3K9me-dependent silenced state...
March 16, 2017: Science
https://www.readbyqxmd.com/read/28302174/feedback-inhibition-of-creb-signaling-by-p38-mapk-contributes-to-the-negative-regulation-of-steroidogenesis
#13
Jiaxin Li, Qian Zhou, Zhuang Ma, Meina Wang, Wen-Jun Shen, Salman Azhar, Zhigang Guo, Zhigang Hu
BACKGROUND: Steroidogenesis is a complex, multi-steps biological process in which, cholesterol precursor is converted to steroids in a tissue specific and tropic hormone dependent manner. Given that steroidogenesis is achieved by coordinated functioning of multiple tissue specific enzymes, many steroids intermediates/metabolites are generated during this process. Both the steroid products as well as major lipoprotein cholesterol donor, high-density lipoprotein 3 (hHDL3) have the potential to negatively regulate steroidogenesis via increased oxidative stress/reactive oxygen species (ROS) generation...
March 16, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28299464/knockdown-of-krt17-by-sirna-induces-antitumoral-effects-on-gastric-cancer-cells
#14
Mihaela Chivu-Economescu, Denisa L Dragu, Laura G Necula, Lilia Matei, Ana Maria Enciu, Coralia Bleotu, Carmen C Diaconu
BACKGROUND: Keratin 17 (KRT17) was shown to be an important molecular marker for predicting the carcinogenesis, progression, and prognosis of various cancer types. Our previous studies identified KRT17 as a possible biomarker for gastric cancer by gene microarray, with an elevated expression that occurred early during tumorigenesis and increased during tumor progression. Based on these findings, we aimed to investigate KRT17 biological functions in gastric adenocarcinoma and its possible use as a rational molecular target for anticancer therapy...
March 15, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28292834/functional-connectivity-of-multiple-brain-regions-required-for-the-consolidation-of-social-recognition-memory
#15
Toshiyuki Tanimizu, Justin W Kenney, Emiko Okano, Kazune Kadoma, Paul W Frankland, Satoshi Kida
Social recognition memory is an essential and basic component of social behavior to discriminate familiar and novel animals/humans. Previous studies have shown the importance of several brain regions for social recognition memories; however, the mechanisms underlying the consolidation of social recognition memory at the molecular and anatomic levels remain unknown. Here, we show a brain network necessary for the generation of social recognition memory in mice. A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory...
March 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28291344/first-bispecific-inhibitors-of-the-epidermal-growth-factor-receptor-kinase-and-the-nf-%C3%AE%C2%BAb-activity-as-novel-anti-cancer-agents
#16
Mostafa M Hamed, Sarah S Darwish, Jennifer Herrmann, Ashraf H Abadi, Matthias Engel
The activation of the NF-κB transcription factor is a major adaptive response induced upon treatment with EGFR kinase inhibitors, leading to the emergence of resistance in non-small cell lung cancer and other tumor types. To suppress this survival mechanism, we developed new thiourea quinazoline derivatives that are dual inhibitors of both EGFR kinase and the NF-κB activity. Optimization of the hit compound, identified in a NF-κB reporter gene assay, led to compound 9b, exhibiting a cellular IC50 for NF-κB inhibition of 0...
March 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28288932/inhibition-of-jnk-by-pi-class-of-glutathione-s-transferase-through-pka-creb-pathway-is-associated-with-carnosic-acid-protection-against-6-hydroxydopamine-induced-apoptosis
#17
Chia-Yuan Lin, Ru-Huei Fu, Ruey-Hwang Chou, Jing-Hsien Chen, Chi-Rei Wu, Shu-Wei Chang, Chia-Wen Tsai
Pi class of glutathione S-transferase (GST) is known to suppress c-Jun N-terminal kinase (JNK)-related apoptosis through protein-protein interactions. Moreover, signaling by PKA/cAMP response element binding protein (CREB) is necessary for GSTP up-regulation. This study explored whether carnosic acid (CA) from rosemary prevents 6-hydroxydopamine (6-OHDA)-induced neurotoxicity by inhibition of JNK through GSTP via PKA/CREB signaling. Results indicated that the GSTP protein was increased in SH-SY5Y cells treated with CA for 18 and 24 h...
March 10, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28287161/angiopoietin-like-4-mediates-colonic-inflammation-by-regulating-chemokine-transcript-stability-via-tristetraprolin
#18
Terri Phua, Ming Keat Sng, Eddie Han Pin Tan, Dickson Shao Liang Chee, Yinliang Li, Jonathan Wei Kiat Wee, Ziqiang Teo, Jeremy Soon Kiat Chan, Maegan Miang Kee Lim, Chek Kun Tan, Pengcheng Zhu, Velmurugesan Arulampalam, Nguan Soon Tan
Many gastrointestinal diseases exhibit a protracted and aggravated inflammatory response that can lead to hypercytokinaemia, culminating in extensive tissue damage. Recently, angiopoietin-like 4 (ANGPTL4) has been implicated in many inflammation-associated diseases. However, how ANGPTL4 regulates colonic inflammation remains unclear. Herein, we show that ANGPTL4 deficiency in mice (ANGPTL4(-/-)) exacerbated colonic inflammation induced by dextran sulfate sodium (DSS) or stearic acid. Microbiota was similar between the two genotypes prior DSS challenge...
March 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28283909/map-kinase-p38-is-a-novel-target-of-cacybp-sip-phosphatase
#19
Agnieszka M Topolska-Woś, Sara Rosińska, Anna Filipek
Mitogen-activated protein (MAP) kinases are important players in cellular signaling pathways. Recently, it has been shown that CacyBP/SIP serves as a phosphatase for one of the MAP kinases, ERK1/2. Through dephosphorylation of this kinase CacyBP/SIP modulates the transcriptional activity of Elk-1 and the activity of the CREB-BDNF pathway. In this work, using NB2a cell lysate and recombinant proteins, we show that CacyBP/SIP binds and dephosphorylates another member of the MAP kinase family, p38. Analysis of recombinant full-length CacyBP/SIP and its three major domains, N-terminal, middle CS and C-terminal SGS, indicates that the middle CS domain is responsible for p38 dephosphorylation...
March 10, 2017: Amino Acids
https://www.readbyqxmd.com/read/28282971/brain-derived-neurotrophic-factor-promotes-human-granulosa-like-tumor-cell-steroidogenesis-and-proliferation-by-activating-the-fsh-receptor-mediated-signaling-pathway
#20
Min Xie, Meiling Li, Ji Zhou, Xiaomeng Ding, Yidan Shao, Jun Jing, Yuxiu Liu, Bing Yao
Brain-derived neurotrophic factor (BDNF) and FSH receptor (FSHR) are expressed in ovarian granulosa cells, and play important roles in regulating follicle growth and oocyte maturation. Studies have linked the BDNF-associated signaling pathway to FSHR mRNA expression in the regulation of follicle development, but the mechanisms remain unknown. In the current study, we found that BDNF stimulated the secretion of estradiol and progesterone, and increased the proliferation of KGN cells (human granulosa-like tumor cell line)...
December 2017: Scientific Reports
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