No abstract available.
Carcinoma, Squamous Cell ; Cyclic AMP Response Element-Binding Protein ; Epithelial Cells

Functioning adrenal cortical tumors are originated form a distinct zone(zonna glomerulosa, zonna fasciculata or zonna reticularis) or the transitonal zone of adrenal gland. Each zone of the gland is regulated by their specific hormons or cytokines, and their signal transduction systems are different. The oncogenes of many endocrine tumors were mutated proteins involved in signal transduction, however gip is the only reported oncogene in adrenal cortical tumors. Therefore we decided to reevaluate whether gsp might be detected as an oncogene in several different functioning adrenal tumors, and we also tested whether CREB protein is a tentative oncogene or not. In our study, gsp was not detected in 13 patients, however gip was not also detected unexpectedly. There were no mutations in the phosporylation site of CREB("P" box) in adrenal cushing syndrome. We concluded that gip was not a oncogene detected frequently in adrenal cortical tumor, and CREB protein was not considered as a tentative oncogen, because there might be no amplification of the signals due to its extreme distal component of PKA or PKC system.
Adrenal Glands ; Cushing Syndrome ; Cyclic AMP Response Element-Binding Protein ; Cytokines ; Humans ; Oncogenes ; Signal Transduction

Poria is an important medicine for inducing diuresis to drain dampness from the middle energizer. However, the specific effective components and the potential mechanism of Poria remain largely unknown. To identify the effective components and the mechanism of Poria water extract (PWE) to treat dampness stagnancy due to spleen deficiency syndrome (DSSD), a rat model of DSSD was established through weight-loaded forced swimming, intragastric ice-water stimulation, humid living environment, and alternate-day fasting for 21 days. After 14 days of treatment with PWE, the results indicated that PWE increased fecal moisture percentage, urine output, D-xylose level and weight; amylase, albumin, and total protein levels; and the swimming time of rats with DSSD to different extents. Eleven highly related components were screened out using the spectrum-effect relationship and LC-MS. Mechanistic studies revealed that PWE significantly increased the expression of serum motilin (MTL), gastrin (GAS), ADCY5/6, p-PKAα/β/γ cat, and phosphorylated cAMP-response element binding protein in the stomach, and AQP3 expression in the colon. Moreover, it decreased the levels of serum ADH, the expression of AQP3 and AQP4 in the stomach, AQP1 and AQP3 in the duodenum, and AQP4 in the colon. PWE induced diuresis to drain dampness in rats with DSSD. Eleven main effective components were identified in PWE. They exerted therapeutic effect by regulating the AC-cAMP-AQP signaling pathway in the stomach, MTL and GAS levels in the serum, AQP1 and AQP3 expression in the duodenum, and AQP3 and AQP4 expression in the colon.
Animals ; Rats ; Poria ; Spleen ; Albumins ; Chromatography, Liquid ; Cyclic AMP Response Element-Binding Protein

Memory is one of the most important mental mechanisms which is crucial for us to adapt to environmental surroundings and to maintain our identity. The neurobiological mechanisms for memory are based upon the synaptic plasticity that involve both functional and structural changes at the synapses in the neural circuits participating in learning and memory. Memory is not a single process but has two forms of short-term and long-term memory that are two independent but overlapping processes that blend into one another. The short-term memory depends upon the functional change of synaptic strength but the long-term memory requires anatomic changes of synapses in the neural circuit. Memory storage seems to use elements of a common genetic switch, involving cyclic adenosine monophospate (cAMP)-dependent protein kinase, mitogen activated protein kinase, and cAMP response element-binding protein, to convert short-term memory into long-term memory.
Adenosine ; Cyclic AMP Response Element-Binding Protein ; Learning ; Memory* ; Memory, Long-Term ; Memory, Short-Term ; Plastics ; Protein Kinases ; Synapses

BACKGROUND: The canonical Wnt/β-catenin signaling pathway is a fundamental regulatory system involved in various biological events. ICG-001 selectively blocks the interaction of β-catenin with its transcriptional co-activator cyclic AMP response element-binding protein (CBP). Recent studies have provided convincing evidence of the inhibitory effects of ICG-001 on Wnt-driven disease models, such as organ fibrosis, cancer, acute lymphoblastic leukemia, and asthma. However, the effects of ICG-001 in atopic dermatitis (AD) have not been investigated. OBJECTIVE: To investigate whether β-catenin/CBP-dependent signaling was contributed in the pathogenesis of AD and ICG-001 could be a therapeutic agent for AD. METHODS: We examined the effects of ICG-001 in an AD-like murine model generated by repeated topical application of the hapten, oxazolone (Ox). ICG-001 or vehicle alone was injected intraperitoneally every day during the development of AD-like dermatitis arising from once-daily Ox treatment. RESULTS: Ox-induced AD-like dermatitis characterized by increases in transepidermal water loss, epidermal thickness, dermal thickness accompanied by increased myofibroblast and mast cell counts, and serum levels of thymic stromal lymphopoietin and thymus and activation-regulated chemokine, and decreases in stratum corneum hydration, were virtually normalized by the treatment with ICG-001. Elevated serum levels of periostin tended to be downregulated, without statistical significance. CONCLUSION: These results suggest that β-catenin/CBP-dependent signaling might be involved in the pathogenesis of AD and could be a therapeutic target.
Animals ; Asthma ; Chemokine CCL17 ; Cyclic AMP Response Element-Binding Protein ; Cyclic AMP ; Dermatitis ; Dermatitis, Atopic ; Fibrosis ; Mast Cells ; Mice ; Myofibroblasts ; Oxazolone ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Water

OBJECTIVE: The hallmark of anxiety disorders is excessive fear. Previous studies have suggested that selective neural projections from Basal nucleus of stria terminalis (BNST) to amygdala and vice-versa precisely control the fear learning process. However the exact mechanism how the BNST controls fear consolidation and its extinction is largely unknown. In the present study we observed the changes in the BNST sub-regions following fear conditioning and its extinction. METHODS: The change in the number of positive neurons was determined by immunohistochemistry for Acetyl H3 (Histone 3), Acetyl H4 (Histone 4), cAMP response element binding Protein (CBP) and c-fos in three sub-regions of the BNST namely the anterio-lateral BNST (STLP) and anterio-medial BNST (STMA), and lateral-ventral BNST (STLV) of rats subjected to auditory fear conditioning and extinction. RESULTS: We found significant increase in the number of CBP, acetyl H3 and acetyl H4 positive neurons in the STMA and STLV but not in the STLP after fear conditioning. However, following fear extinction the number of CBP, acetyl H3 and acetyl H4 positive neurons increased significantly in the STLP but not in the STMA and STLV. Similar changes were observed in the number of c-fos positive neurons after fear consolidation and extinction. CONCLUSION: The results from this study suggest that the differential histone acetylation in the different sub-regions of the BNST following fear learning and its extinction may be responsible for changes in the neuronal activation patterns resulting in either fear or less fear.
Acetylation* ; Amygdala ; Animals ; Anxiety Disorders ; Cyclic AMP Response Element-Binding Protein ; Histones* ; Immunohistochemistry ; Learning ; Neurons ; Rats ; Septal Nuclei*

cAMP response element-binding protein (CREB), a transcription factor, has been shown to play a central role in memory formation, and its involvement in this process has been investigated using a wide range of animal models, from nematodes to higher animals. Various CREB mutant mice have been developed and investigated. Several types of mutant mice with loss of CREB function have impaired memory formation and long-term potentiation (LTP), suggesting that CREB plays essential roles in these processes. To characterize the roles of CREB in memory formation and LTP further, mutant mice displaying gain of CREB function have been generated and analyzed. Importantly, CREB-DIEDML mice and CREB-Y134F mice showed enhanced memory formation, whereas CREB-VP16 mice displayed a lowered threshold of long-lasting LTP (L-LTP) induction, strongly suggesting that CREB functions as a positive regulator of memory formation and LTP. In this review, I focus on the effects of the genetic activation of CREB in LTP and memory formation and summarize previous findings.
Animals ; Brain-Derived Neurotrophic Factor ; Cyclic AMP Response Element-Binding Protein ; Long-Term Potentiation ; Memory ; Mice ; Models, Animal ; Transcription Factors

In the present study, we first examined whether the changes in the DNA binding activities of the transcription factors, cAMP response element binding protein (CREB) and activator protein-1 (AP-1) mediate the long-term effects of morphine in differentiated SH-SY5Y human neuroblastoma cells. The increases in CREB and AP-1 DNA binding activities were time-dependent up to 6 days of morphine treatment (1, 4, and 6 days). However, the significant reduction in the DNA binding activities of CREB and AP-1 was observed after 10 days of chronic morphine (10 muM) administration. Secondly, we examined whether the changes of CREB and AP-1 DNA binding activities could be modulated by dopamine and haloperidol. Dopamine cotreatment moderately increased the levels of the CREB and AP-1 DNA binding activities induced by 10 days of chronic morphine treatment, and haloperidol cotreatment also resulted in a moderate increase of the CREB and AP-1 DNA binding activities. However, dopamine or haloperidol only treatment showed a significant increase or decrease of the CREB and AP-1 DNA binding activities, respectively. In the case of acute morphine treatment, the CREB and AP-1 DNA binding activities were shown to decrease in a time-dependent manner (30, 60, 90, and 120 min). Taken these together, in differentiated SH-SY5Y cells, morphine tolerance seems to involve simultaneous changes of the CREB and AP-1 DNA binding activities. Our data also suggest the possible involvement of haloperidol in prevention or reversal of morphine tolerance at the transcriptional level.
Cyclic AMP Response Element-Binding Protein ; DNA* ; Dopamine* ; Haloperidol* ; Humans* ; Morphine ; Neuroblastoma* ; Transcription Factor AP-1* ; Transcription Factors

OBJECTIVE: To study the expression level of cAMP response element-binding protein (CREB) in children with recurrent wheezing under three years of age and its effect on the expression of the serum orosomucoid 1-like protein 3 (ORMDL3) gene. METHODS: Thirty-six children with recurrent wheezing under three years of age who visited the hospital from June 2017 to June 2019 were selected as the recurrent wheezing group. Twenty-four healthy children from physical examination were selected as the control group. The CREB expression level in peripheral blood was measured by quantitative real-time PCR. Human bronchial epithelial cells (BEAS-2B) were cultured, and dual-luciferase reporter assay and quantitative real-time PCR were used to investigate the effects of overexpression and siRNA interference of CREB on the promoter activity and mRNA expression of the ORMDL3 gene in the BEAS-2B cells. RESULTS: The expression level of CREB in the recurrent wheezing group was significantly higher than that in the control group (P<0.001). In BEAS-2B cells, overexpression of CREB significantly up-regulated the promoter activity and mRNA expression of the ORMDL3 gene (P<0.05), while siRNA interference of CREB significantly reduced the promoter activity and mRNA expression of the ORMDL3 gene (P<0.05). CONCLUSIONS The expression of CREB is increased in children with recurrent wheezing, and CREB may be involved in the pathogenesis of recurrent wheezing by regulating expression of the ORMDL3 gene.
Child, Preschool ; Cyclic AMP Response Element-Binding Protein ; Epithelial Cells ; Humans ; Membrane Proteins ; genetics ; Promoter Regions, Genetic ; Respiratory Sounds

Taurochenodeoxycholic acid (TCDCA) is one of the main effective components of bile acid, playing critical roles in apoptosis and immune responses through the TGR5 receptor. In this study, we reveal the interaction between TCDCA and TGR5 receptor in TGR5-knockdown H1299 cells and the regulation of inflammation via the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element binding (CREB) signal pathway in NR8383 macrophages. In TGR5-knockdown H1299 cells, TCDCA significantly activated cAMP level via TGR5 receptor, indicating TCDCA can bind to TGR5; in NR8383 macrophages TCDCA increased cAMP content compared to treatment with the adenylate cyclase (AC) inhibitor SQ22536. Moreover, activated cAMP can significantly enhance gene expression and protein levels of its downstream proteins PKA and CREB compared with groups of inhibitors. Additionally, TCDCA decreased tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8 and IL-12 through nuclear factor kappa light chain enhancer of activated B cells (NF-κB) activity. PKA and CREB are primary regulators of anti-inflammatory and immune response. Our results thus demonstrate TCDCA plays an essential anti-inflammatory role via the signaling pathway of cAMP-PKA-CREB induced by TGR5 receptor.
Animals ; Cell Line ; Cyclic AMP/metabolism* ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Cyclic AMP-Dependent Protein Kinases/metabolism* ; Cytokines/metabolism* ; Humans ; Inflammation ; Macrophages ; Rats ; Receptors, G-Protein-Coupled/metabolism* ; Signal Transduction/drug effects* ; Taurochenodeoxycholic Acid/pharmacology*