Effects of A-CREB, a dominant negative inhibitor of CREB, on the expression of c-fos and other immediate early genes in the rat SON during hyperosmotic stimulation in vivo

Lubelski, Daniel; Ponzio, Todd A.; Gainer, Harold

doi:10.1016/j.brainres.2011.10.033

Cited by 17 publications

(12 citation statements)

References 55 publications

(90 reference statements)

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“…CREB and its family members contain a bZIP domain that mediates DNA binding and dimerization to CRE site and enhances gene transcription (41)(42)(43). Transfection of our neuronal cultures with a dominantnegative inhibitor of CREB (A-CREB), which interacts with CREB at its bZIP domain binding (44,45), resulted in a significant decrease in the transgenic PTGS2 promoter-driven luciferase expression (Fig. 7), suggesting an important role for CREB in regulation of constitutive COX-2 expression in neurons.…”

Section: Discussionmentioning

confidence: 90%

Spontaneous Glutamatergic Synaptic Activity Regulates Constitutive COX-2 Expression in Neurons OPPOSING ROLES FOR THE TRANSCRIPTION FACTORS CREB (cAMP RESPONSE ELEMENT BINDING) PROTEIN AND Sp1 (STIMULATORY PROTEIN-1)

Hewett

Shi

Gong

et al. 2016

Journal of Biological Chemistry

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Edited by Paul E. FraserBurgeoning 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. Extracts from the whole brain and from the cerebral cortex, hippocampus, and olfactory bulbs exhibited high luciferase activity. Moreover, constitutive COX-2 expression and luciferase activity were detected in cortical neurons, but not in cortical astrocytes, cultured from wild-type and transgenic mice, respectively. Constitutive COX-2 expression depended on spontaneous but not evoked excitatory synaptic activity and was shown to be N-methyl-D-aspartate receptor-dependent. Constitutive promoter activity was reduced in neurons transfected with a dominant-negative cAMP response element binding protein (CREB) and was eliminated by mutating the CRE-binding site on the COX-2 promoter. However, mutation of the stimulatory protein-1 (Sp1)-binding site resulted in an N-methyl-D-aspartate receptor-dependent enhancement of COX-2 promoter activity. Basal binding of the transcription factors CREB and Sp1 to the native neuronal COX-2 promoter was confirmed. In toto, our data suggest that spontaneous glutamatergic synaptic activity regulates constitutive neuronal COX-2 expression via Sp1 and CREB protein-dependent transcriptional mechanisms.The first committed reaction in the metabolism of arachidonic acid to prostaglandins and thromboxanes is catalyzed by two related heme-containing bis-oxygenases, cyclooxygenase (COX) 1 and 2. These enzymes share 90% similarity in amino acid sequence and exhibit nearly identical enzyme kinetics (1, 2). Both catalyze two separate reactions, the first metabolizing arachidonic acid to PGG 2 3 (cyclooxygenase reaction), an intermediate that is subsequently reduced in the second reaction to the product, PGH 2 (peroxidase reaction). PGH 2 is the substrate for various synthases that generate individual biologically active prostaglandins and thromboxanes, often in a cell typespecific manner (3). Although both metabolize arachidonic acid to PGH 2 , the transcriptional regulation of each isoform differs. The PTGS1 gene encoding COX-1 lacks a TATA box motif in its 5Ј promoter region and is generally constitutively active in cells (4, 5). In contrast, the promoter regulatory region of the PTGS2 gene encoding COX-2 is not typically active but can be strongly and rapidly induced under specific...

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Section: Discussionmentioning

confidence: 90%

Spontaneous Glutamatergic Synaptic Activity Regulates Constitutive COX-2 Expression in Neurons OPPOSING ROLES FOR THE TRANSCRIPTION FACTORS CREB (cAMP RESPONSE ELEMENT BINDING) PROTEIN AND Sp1 (STIMULATORY PROTEIN-1)

Hewett

Shi

Gong

et al. 2016

Journal of Biological Chemistry

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“…There are various studies about CREB1-FOS regulation relationship. Lubelski et al reported that complete inhibition of CREB1 binding to DNA only decreased by 20% of FOS activity (Lubelski, Ponzio, & Gainer, 2012). Mutation in the GNB3 gene was accompanied by essential hypertension and obesity.…”

Section: Discussionmentioning

confidence: 99%

Introducing Genes With Significant Role in Migraine: An Interactomic Approach

Azodi

Tavirani

Robati

2019

Basic Clin. Neurosci. J.

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Migraine is a severe kind of headache with the chance hereditary of 50%. Molecular studies can promote understanding of migraine pathophysiology. One of which is bioinformatics approach that could provide additional information related to the identified biomarkers. Methods: In this research, migraine genes are studies in terms of interaction pattern to introduce important individuals. Through STRING database Plug-in in Cytoscape, candidate genes for migraine were retrieved and analyzed by related applications. Based on centrality and action types (expression, activation, and inhibition) genes were screened. Results: Numbers of 33 central genes including seven hub-bottlenecks were identified which 70% of central genes were involved in expression action with each other. Activation was dominate action relative to inhibition between the central genes. Conclusion: The finding indicates that insulin is the most important gene relative to migraine. It seems regulation of metabolism play critical role in control of migraine.

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“…ERK1/2 is activated in the PVN when ACTH is released due to stress, which may indicate that ERK1/2 releases ACTH from the PVN (195). We suspect that ERK1/2 activation within the periphery of the SFO may signal (possibly through ANG) to activate ERK1/2 within the PVN to release ACTH and AVP, and to activate CREB within the SON to release AVP (195,199,200). The fluid phenotype of sRA mice is corrected with adrenalectomy and attenuated with spironolactone, which implies that ACTH is acting on the adrenals to mediate the fluid balance effects of brain-RAS hyperactivity or is a parallel pathway with SFO PKC-α.…”

Section: Discussionmentioning

confidence: 99%

“…ROS, ER stress the MAPK pathway, and CREB should be investigated in the SFO, PVN, and RVLM since they have been shown to mediate central ANG-II hypertension (40,127,141,154,156,(195)(196)(197). CREB in the PVN and SON should also be examined since these factors mediate vasopressin release, and the hypertension of sRA mice has been shown to occur through vasopressin (98,169,(198)(199)(200). In studies here, we sought to determine whether production of ANG from the SFO increased ERK1/2 and/or CREB activity in the SFO to stimulate the PVN or SON.…”

Section: Chapter 4: Conclusionmentioning

confidence: 99%

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Molecular mechanisms of brain-ras hyperactivity upon fluid balance, and sufficiency of angiotensin production from the subfornical organ to affect fluid balance

Coble¹

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___________________________________ Kamal Rahmouni ii ACKNOWLEDGMENTS I would like to acknowledge my mentor, Dr. Curt Sigmund, for given the opportunity to develop myself as a scientist, and for supplying me with the appropriate guidance. I would like to acknowledge, Dr. Justin Grobe, for also guiding me on my path of training. I would also like to acknowledge the University of Iowa Medical Scientist Training Program for believing in me to become a physician-scientist. Finally, I would like to acknowledge my parents, Laura and Paul Coble, for their unbound love and support.iii ABSTRACT Fluid balance is critical for cells to maintain at homeostasis as disturbances in it can disrupt cell function and consequently the physiology of an organism. Fluid loss for an organism can be classified as either intra-or extracellular, and it appears that different mechanisms have developed to restore homeostasis after intra-or extracellular dehydration. The renin-angiotensin system (RAS) has been shown to be an important mediator of extracellular dehydration induced fluid intake. Various lines of evidence have demonstrated the importance of the subfornical organ (SFO) to mediate fluid intake, especially due to the RAS, and we have shown that production and action of angiotensin (ANG) at the SFO is necessary for fluid intake due to ANG within the brain. PKC, specifically PKC-α, is demonstrated here to be a necessary and sufficient effector in the SFO to mediate brain ANG polydipsia. Production of ANG from the SFO is also shown to be sufficient to increase fluid intake through the angiotensin-II type 1 (AT 1 R) receptor and PKC. While production of ANG from the SFO is sufficient to increase fluid intake it is not sufficient to increase blood pressure or sodium appetite. Thus, production and action of ANG to activate PKC-α is both necessary and sufficient to increase fluid intake, and the fluid and pressor phenotypes of brain ANG through the SFO can be separated.

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Effects of A-CREB, a dominant negative inhibitor of CREB, on the expression of c-fos and other immediate early genes in the rat SON during hyperosmotic stimulation in vivo

Cited by 17 publications

References 55 publications

Spontaneous Glutamatergic Synaptic Activity Regulates Constitutive COX-2 Expression in Neurons OPPOSING ROLES FOR THE TRANSCRIPTION FACTORS CREB (cAMP RESPONSE ELEMENT BINDING) PROTEIN AND Sp1 (STIMULATORY PROTEIN-1)

Spontaneous Glutamatergic Synaptic Activity Regulates Constitutive COX-2 Expression in Neurons OPPOSING ROLES FOR THE TRANSCRIPTION FACTORS CREB (cAMP RESPONSE ELEMENT BINDING) PROTEIN AND Sp1 (STIMULATORY PROTEIN-1)

Introducing Genes With Significant Role in Migraine: An Interactomic Approach

Molecular mechanisms of brain-ras hyperactivity upon fluid balance, and sufficiency of angiotensin production from the subfornical organ to affect fluid balance

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