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https://www.readbyqxmd.com/read/27908835/modulation-of-signaling-through-gpcr-camp-pka-pathways-by-pde4-depends-on-stimulus-intensity-possible-implications-for-the-pathogenesis-of-acrodysostosis-without-hormone-resistance
#1
Emmanuelle Motte, Catherine Le Stunff, Claire Briet, Nicolas Dumaz, Caroline Silve
In acrodysostosis without hormone resistance, a disease caused by phosphodiesterase (PDE)-4D mutations, increased PDE activity leads to bone developmental defects but with normal renal responses to PTH. To identify potential mechanisms for these disparate responses, we compared the effect of PDE activity on hormone signaling through the GPCR-Gsα-cAMP-PKA pathway in cells from two lineages, HEK-293 cells stably overexpressing PTH1R (HEKpthr) and human dermal fibroblasts, including studies evaluating cAMP levels using an Epac-based BRET-sensor for cAMP (CAMYEL)...
November 28, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27908782/adaptive-responses-of-neuronal-mitochondria-to-bioenergetic-challenges-roles-in-neuroplasticity-and-disease-resistance
#2
REVIEW
Sophia M Raefsky, Mark P Mattson
An important concept in neurobiology is "neurons that fire together, wire together" which means that the formation and maintenance of synapses is promoted by activation of those synapses. Very similar to the effects of the stress of exercise on muscle cells, emerging findings suggest that neurons respond to activity by activating signaling pathways (e.g., Ca(2+), CREB, PGC-1α, NF-κB) that stimulate mitochondrial biogenesis and cellular stress resistance. These pathways are also activated by aerobic exercise and food deprivation, two bioenergetic challenges of fundamental importance in the evolution of the brains of all mammals, including humans...
November 28, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27903866/nigral-dopaminergic-pak4-prevents-neurodegeneration-in-rat-models-of-parkinson-s-disease
#3
So-Yoon Won, Mee-Hee Park, Soon-Tae You, Seung-Won Choi, Hyong-Kyu Kim, Catriona McLean, Suk-Chul Bae, Sang Ryong Kim, Byung Kwan Jin, Kun Ho Lee, Eun-Young Shin, Eung-Gook Kim
Parkinson's disease (PD) is characterized by progressive loss of dopaminergic (DA) neurons in the substantia nigra. No neuroprotective treatments have successfully prevented the progression of this disease. We report that p21-activated kinase 4 (PAK4) is a key survival factor for DA neurons. We observed PAK4 immunoreactivity in rat and human DA neurons in brain tissue, but not in microglia or astrocytes. PAK4 activity was markedly decreased in postmortem brain tissue from PD patients and in rodent models of PD...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27902946/social-regulation-of-the-lymph-node-transcriptome-in-rhesus-macaques-macaca-mulatta
#4
K Chun, J P Capitanio, D M Lamkin, E K Sloan, J M G Arevalo, S W Cole
Previous research has shown that adverse social conditions may promote a conserved transcriptional response to adversity (CTRA) involving up-regulation of proinflammatory gene expression and down-regulation of Type I interferon anti-viral genes in circulating blood cells. However, the impact of social conditions on lymphoid tissue gene regulation remains largely unexplored. This project assessed how social instability in adult male rhesus macaques (N=10, 5 in unstable, and 5 in stable social conditions) might regulate gene expression within secondary lymphoid tissue (lymph nodes; LN)...
November 14, 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/27901267/binge-alcohol-intake-after-hypergravity-stress-sustainably-decreases-ampk-and-transcription-factors-necessary-for-hepatocyte-survival
#5
Sang Gil Lee, Hong Min Wu, Chan Gyu Lee, Choong Sik Oh, So Won Chung, Sang Geon Kim
BACKGROUND: Binge alcohol consumption elicits mitochondrial dysfunction in hepatocytes. An understanding of the effect of ethanol (EtOH) exposure after hypergravity stress on liver function may assist in the implementation of pathophysiological countermeasures for aerospace missions. This study investigated whether a combination of hypergravity stress and binge alcohol intake has a detrimental effect on AMP-activated protein kinase (AMPK) and other molecules necessary for hepatocyte survival...
November 30, 2016: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/27891679/adenylyl-cyclase-3-adenylyl-cyclase-associated-protein-1-cap1-complex-mediates-the-anti-migratory-effect-of-forskolin-in-pancreatic-cancer-cells
#6
Sierra Quinn, Sarai Graves, Clayton Dains-McGahee, Emilee Friedman, Humma Hassan, Piotr Witkowski, Maria E Sabbatini
Pancreatic cancer is one of the most lethal human malignancies. A better understanding of the intracellular mechanism of migration and invasion is urgently needed to develop treatment that will suppress metastases and improve overall survival. Cyclic adenosine monophosphate (cyclic AMP) is a second messenger that has shown to regulate migration and invasion of pancreatic cancer cells. The rise of cyclic AMP suppressed migration and invasion of pancreatic ductal adenocarcinoma cells. Cyclic AMP is formed from cytosolic ATP by the enzyme adenylyl cyclase (AC)...
November 27, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27889579/protective-effects-of-high-tryptophan-diet-on-aging-induced-passive-avoidance-impairment-and-hippocampal-apoptosis
#7
Giuseppe Musumeci, Paola Castrogiovanni, Marta Anna Szychlinska, Rosa Imbesi, Carla Loreto, Sergio Castorina, Salvatore Giunta
In our previous work we have shown that L-Tryptophan (TrP) enriched diet prevents the age-induced decline of hippocampal Serotonin (5-HT) production. Considering that loss or reduction in 5-HT neurotransmission may contribute to age-related cognitive decline, here we have investigated the effect of such diet on passive avoidance (PA) behavior, cell death, pro- and anti- apoptotic molecules (BAX, Bcl-2 and Caspase-3) and an important transcription factor involved in synaptic plasticity and memory (CREB). The increase in 5-HT neurotransmission in the Hippocampus (Hp) of aged rats was induced by 1 month of high TrP administration...
November 23, 2016: Brain Research Bulletin
https://www.readbyqxmd.com/read/27889175/inhibition-of-adenylyl-cyclase-in-the-spinal-cord-alleviates-painful-diabetic-neuropathy-in-zucker-diabetic-fatty-rats
#8
Hao Feng, Guodong Lu, Qingsong Li, Zhonghao Liu
OBJECTIVES: Diabetic neuropathy is the most common complication of both type 1 and type 2 diabetes. In this study, we tested the hypotheses that impaired Gi protein expression/function in the spinal cord is associated with the development of painful neuropathy in people with type 2 diabetes and that reduction of cyclic adenosine monophosphate (cAMP) production by inhibiting adenylyl cyclase in the spinal cord can alleviate diabetic neuropathy. METHODS: To this end, we examined the levels of cAMP, cAMP-dependent protein kinase (PKA) and cAMP response element-binding protein (CREB) in the spinal cord after the development of neuropathic pain in Zucker diabetic fatty (ZDF) rats with type 2 diabetes...
November 23, 2016: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/27885183/-osteoporosis-and-mechano-biosciences
#9
Toshio Matsumoto
Mechanical unloading due to long-term bedrest or microgravity during spaceflight causes a devastating influence on bone. Although bisphosphonates can prevent bone loss and hypercalciuria by mechanical unloading for up to 6 months, the influence of unloading for longer period of time is unknown. This is because mechanical loading is one of the most important stimuli for bone formation. Mechanical stress activates several intracellular signaling pathways. Among them, activation of stress-activated cation channel by fluid shear stress stimulates ERK-CREB signaling to enhance the expression of fos family transcription factors, which stimulates IL-11 expression in osteoblastic cells...
2016: Clinical Calcium
https://www.readbyqxmd.com/read/27884605/arsenic-induced-activation-of-the-homeodomain-interacting-protein-kinase-2-hipk2-to-camp-response-element-binding-protein-creb-axis
#10
Kazunori Hashimoto, Yoshiaki Tsuji
CREB (cAMP-response element binding protein) plays key transcriptional roles in cell metabolism, proliferation, and survival. Ser133 phosphorylation by protein kinase A (PKA) is a well-characterized CREB activation mechanism. HIPK2 (homeodomain interacting protein kinase 2), a nuclear serine/threonine kinase, activates CREB through Ser271 phosphorylation; however, the regulatory mechanism remains uncharacterized. Transfection of CREB in HEK293 cells together with the kinase demonstrated that HIPK2 phosphorylated CREB at Ser271 but not Ser133, likewise PKA phosphorylated CREB at Ser133 but not Ser271, suggesting two distinct CREB regulatory mechanisms by HIPK2 and PKA...
November 21, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27882154/kai-xin-san-a-traditional-chinese-medicine-formulation-exerts-antidepressive-and-neuroprotective-effects-by-promoting-pcreb-upstream-pathways
#11
Xian-Zhe Dong, Dong-Xiao Wang, Bing-Ying Yu, Ping Liu, Yuan Hu
Kai-Xin-San (KXS) is a traditional Chinese medicine that has been widely used for the treatment of emotion-related disease. However, the underlying mechanism remains largely unknown. The present study aimed to examine whether phospho-cAMP response element-binding protein (pCREB) and upstream components, such as extracellular signal-regulated kinase (ERK), phospho-ERK (pERK), phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), glycogen synthase kinase 3β (GSK3β) and pGSK3β are associated with the antidepressive effect of KXS...
November 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/27882071/pigmentation-effect-of-rice-bran-extracted-minerals-comprising-soluble-silicic-acids
#12
Hyun-Jun Jang, Young-Kwon Seo
Our investigation focused on identifying melanogenesis effect of soluble minerals in rice bran ash extract (RBE) which include orthosilicic acid (OSA). Melanocytes were apparently normal in terms of morphology. It was, however, shown that they were stressed a little in the RBE and OSA added media in aspect of LDH activity. Melanin synthesis and intracellular tyrosinase activity were increased by treatment of RBE which is similar to that of OSA. The Western blotting results showed that TRP-1, tyrosinase, and MITF expression levels were 2-3 times higher in the OSA and RBE groups compared to the control group which promoted melanin synthesis through CREB phosphorylation...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/27881443/exploitation-of-ep300-and-crebbp-lysine-acetyltransferases-by-cancer
#13
Narsis Attar, Siavash K Kurdistani
p300 and CREB-binding protein (CBP), two homologous lysine acetyltransferases in metazoans, have a myriad of cellular functions. They exert their influence mainly through their roles as transcriptional regulators but also via nontranscriptional effects inside and outside of the nucleus on processes such as DNA replication and metabolism. The versatility of p300/CBP as molecular tools has led to their exploitation by viral oncogenes for cellular transformation and by cancer cells to achieve and maintain an oncogenic phenotype...
November 23, 2016: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/27878624/the-creb-deubiquitinating-enzyme-does-not-directly-target-the-crea-repressor-protein-in-aspergillus-nidulans
#14
Md Ashiqul Alam, Niyom Kamlangdee, Joan M Kelly
Ubiquitination/deubiquitination pathways are now recognized as key components of gene regulatory mechanisms in eukaryotes. The major transcriptional repressor for carbon catabolite repression in Aspergillus nidulans is CreA, and mutational analysis led to the suggestion that a regulatory ubiquitination/deubiquitination pathway is involved. A key unanswered question is if and how this pathway, comprising CreB (deubiquitinating enzyme) and HulA (ubiquitin ligase) and other proteins, is involved in the regulatory mechanism...
November 23, 2016: Current Genetics
https://www.readbyqxmd.com/read/27878554/the-involvement-of-the-decrease-of-astrocytic-wnt5a-in-the-cognitive-decline-in-minimal-hepatic-encephalopathy
#15
Saidan Ding, Zhu Xu, Jianjing Yang, Leping Liu, Xueli Huang, Xuebao Wang, Qichuan Zhuge
Wnt signaling plays a key role in neuroprotection and synaptic plasticity. We speculate that the impairment of Wnt signaling may mediate astrocytic neurotrophins (NTs) production and the impairment of Wnt signaling to astrocytic NTs production contributes to the pathogenesis of minimal hepatic encephalopathy (MHE). Here, we found that induction of astrocytic NTs synthesis was by Wnt5a via the calcium/calmodulin-sensitive protein kinase II (CaMK II)-cAMP-response element-binding protein (CREB) pathway in PCAs...
November 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27878552/strength-and-aerobic-exercises-improve-spatial-memory-in-aging-rats-through-stimulating-distinct-neuroplasticity-mechanisms
#16
Thais Ceresér Vilela, Alexandre Pastoris Muller, Adriani Paganini Damiani, Tamires Pavei Macan, Sabrina da Silva, Paula Bortoluzzi Canteiro, Alisson de Sena Casagrande, Giulia Dos Santos Pedroso, Renata Tiscoski Nesi, Vanessa Moraes de Andrade, Ricardo Aurino de Pinho
Aging is associated with impaired cognition and memory and increased susceptibility to neurodegenerative disorders. Physical exercise is neuroprotective; however, the major evidence of this effect involves studies of only aerobic training in young animals. The benefits of other exercise protocols such as strength training in aged animals remains unknown. Here, we investigated the effect of aerobic and strength training on spatial memory and hippocampal plasticity in aging rats. Aging Wistar rats performed aerobic or strength training for 50 min 3 to 4 days/week for 8 weeks...
November 22, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27876882/nr4a1-knockdown-suppresses-seizure-activity-by-regulating-surface-expression-of-nr2b
#17
Yanke Zhang, Guojun Chen, Baobing Gao, Yunlin Li, Shuli Liang, Xiaofei Wang, Xuefeng Wang, Binglin Zhu
Nuclear receptor subfamily 4 group A member 1 (NR4A1), a downstream target of CREB that is a key regulator of epileptogenesis, has been implicated in a variety of biological processes and was previously identified as a seizure-associated molecule. However, the relationship between NR4A1 and epileptogenesis remains unclear. Here, we showed that NR4A1 protein was predominantly expressed in neurons and up-regulated in patients with epilepsy as well as pilocarpine-induced mouse epileptic models. NR4A1 knockdown by lentivirus transfection (lenti-shNR4A1) alleviated seizure severity and prolonged onset latency in mouse models...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27876620/the-gabab-positive-allosteric-modulators-cgp7930-and-gs39783-stimulate-erk1-2-signalling-in-cells-lacking-functional-gabab-receptors
#18
Maria C Olianas, Simona Dedoni, Pierluigi Onali
The present study shows that the GABAB positive allosteric modulators (PAMs) CGP7930 and GS39783 stimulate extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) signalling in cells that do not express functional GABAB receptors. In human SH-SY5Y neuroblastoma cells, CGP7930 and GS39783 induced a time- and concentration-dependent increase in ERK1/2 phosphorylation with potencies similar to those displayed as GABAB PAMs. Conversely, γ-aminobutyric acid and the GABAB receptor agonists (-)baclofen and SKF97541 were completely inactive...
November 19, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27875294/spontaneous-glutamatergic-synaptic-activity-regulates-constitutive-cox-2-expression-in-neurons-opposing-roles-for-the-transcription-factors-creb-and-sp1
#19
Sandra J Hewett, Jingxue Shi, Yifan Gong, Krishnan Dhandapani, Carol Pilbeam, James A Hewett
Burgeoning evidence supports a role for cyclooxygenase metabolites in regulating membrane excitability in various forms of synaptic plasticity. Two cyclooxygenases, COX-1 and COX-2, catalyze the initial step in the metabolism of arachidonic acid to prostaglandins. COX-2 is generally considered inducible, but in glutamatergic neurons in some brain regions, including the cerebral cortex, it is constitutively expressed. However, the transcriptional mechanisms by which this occurs have not been elucidated. Here, we used quantitative PCR and also analyzed reporter gene expression in a mouse line carrying a construct consisting of a portion of the proximal promoter region of the mouse COX-2 gene upstream of luciferase cDNA to characterize COX-2 basal transcriptional regulation in cortical neurons...
November 14, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27875242/involvement-of-bdnf-trkb-and-erk-creb-axes-in-nitroglycerin-induced-rat-migraine-and-effects-of-estrogen-on-these-signals-in-the-migraine
#20
Jiu-Qing Guo, Hui-Hui Deng, Xiao Bo, Xiao-Su Yang
Migraine is a highly prevalent headache disorder especially in women. Brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinases (TrkB), as well as extracellular signal-regulated kinase (ERK) and its downstream target c-AMP-responsive element binding protein (CREB) are strongly associated with the transmission of nociceptive information. However, the involvement of these substances in migraine has rarely been examined. In the present study, intraperitoneal injection of nitroglycerin (NTC) successfully induced rat migraine attack, as evidenced by the behavioral testing...
November 14, 2016: Biology Open
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