scholarly journals Transcriptional activation of the haem oxygenase-1 gene by cGMP via a cAMP response element/activator protein-1 element in primary cultures of rat hepatocytes

1998 ◽  
Vol 334 (1) ◽  
pp. 141-146 ◽  
Author(s):  
Stephan IMMENSCHUH ◽  
Vera HINKE ◽  
Andreas OHLMANN ◽  
Susanne GIFHORN-KATZ ◽  
Norbert KATZ ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Primary Cultures ◽  
Rat Hepatocytes ◽  
Protein Kinase G ◽  
Activator Protein 1 ◽  
Camp Response Element ◽  
Response Element ◽  
Activator Protein ◽  
Mrna Induction ◽  
Haem Oxygenase

The expression of the rate-limiting enzyme of haem degradation, haem oxygenase-1 (HO-1), can be induced by various stimuli, including lipopolysaccharide, tumour necrosis factor α and NO. The NO signal can be transmitted by cGMP, therefore this study was aimed at testing the activation of the HO-1 gene by cGMP. In primary cultures of rat hepatocytes, both HO-1 mRNA and protein were induced by the NO donor sodium nitroprusside and 8-bromo-cGMP. The HO-1 mRNA induction by cGMP was prevented by the specific protein kinase G inhibitor KT5823. The cGMP-dependent HO-1 mRNA induction was dose-dependent and transcriptionally regulated, as determined by studies with actinomycin D and a nuclear run-on assay. Cycloheximide lowered the cGMP-dependent induction of HO-1 mRNA to about one half. Luciferase reporter constructs driven by about 800 bp of the 5´-flanking region of the rat HO-1 gene were transiently transfected into primary rat hepatocytes; 8-bromo-cGMP caused a 6-fold induction, which was obliterated by deletion and mutation of the cAMP response element/activator protein-1 (CRE/AP-1) (-665/-654) site. Thus HO-1 induction by cGMP appears to be stimulated by the protein kinase G pathway and may be mediated mainly via a CRE/AP-1 element in the rat HO-1 promoter.

scholarly journals Rapid Nongenomic E2 Effects on p42/p44 MAPK, Activator Protein-1, and cAMP Response Element Binding Protein in Rat White Adipocytes

Endocrinology ◽  
2002 ◽  
Vol 143 (3) ◽  
pp. 930-940 ◽  
Author(s):  
Esther Garcia Dos Santos ◽  
Marie Noëlle Dieudonne ◽  
René Pecquery ◽  
Vincent Le Moal ◽  
Yves Giudicelli ◽  
...  
Keyword(s):  
Binding Protein ◽  
Camp Response Element Binding ◽  
Activator Protein 1 ◽  
Camp Response Element ◽  
Response Element ◽  
Activator Protein ◽  
White Adipocytes ◽  
Element Binding Protein

scholarly journals Identification of human myometrial target genes of the cAMP pathway: the role of cAMP-response element binding (CREB) and modulator (CREMα and CREMτ2α) proteins

2005 ◽  
Vol 34 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Jarrod Bailey ◽  
Alison J Tyson-Capper (née Pollard) ◽  
Kate Gilmore ◽  
Stephen C Robson ◽  
G Nicholas Europe-Finner
Keyword(s):  
Protein Kinase ◽  
Target Genes ◽  
Splice Variants ◽  
Camp Response Element Binding ◽  
Human Myometrium ◽  
Activator Protein 1 ◽  
Nucleic Acid Binding ◽  
Camp Response Element ◽  
Response Element ◽  
Nucleic Acid Binding Proteins

cAMP-response element (CRE) binding (CREB) and modulator (CREM) proteins, activated by protein kinase A-mediated phosphorylation, bind as homo- and heterodimers to promoters containing CRE and activator protein 1 (AP-1) sites to alter target-gene expression. We have previously reported differential expression of CREB and CREM splice variants CREMα and CREMτ2α in human myometrium during pregnancy and labour. Via microarray studies with cultured myometrial cells stably transfected with CREB, CREMα and CREMτ2α cDNAs, CREB affected the expression of 958 genes; 522 being up-regulated and 436 down-regulated. CREMα altered the expression of 118 genes; 71 were increased and 47 decreased. CREMτ2α affected 220 genes; 148 were activated and 72 repressed. Notably, genes affected by CREB, CREMα and CREMτ2α belong to largely discrete groups: less than 9% were affected by more than one factor. Genes involved in regulation of cell death and apoptosis, growth and maintenance, signal transduction, physiological and developmental processes, protein kinase cascades, extracellular matrix, cytoskeleton, cell-cycle regulation, transport, and a variety of enzymes, intracellular components and nucleic acid-binding proteins have been described, many of which are involved in the modulation of myometrial activity during pregnancy and parturition.

scholarly journals Red wine metabolites modulate NF-κB, activator protein-1 and cAMP response element-binding proteins in human endothelial cells

2009 ◽  
Vol 103 (6) ◽  
pp. 807-814 ◽  
Author(s):  
Raffaella Canali ◽  
Raffaella Comitato ◽  
Roberto Ambra ◽  
Fabio Virgili
Keyword(s):  
Endothelial Cells ◽  
Transcription Factors ◽  
Binding Proteins ◽  
Red Wine ◽  
Camp Response Element Binding ◽  
Activator Protein 1 ◽  
Camp Response Element ◽  
Response Element ◽  
Activator Protein ◽  
Tnf Α

We have studied the effect of human serum, collected after red wine consumption (RWS), on TNF-α-dependent activation of transcription factors (NF-κB, activator protein-1 (AP-1) and cAMP response element-binding proteins) and on the expression of selected genes involved in cell adhesion or fibrinolysis processes in human primary endothelial cells (human umbilical vein endothelial cells (HUVEC)). Our data indicate that RWS containing RW metabolites, isolated after 40 min from an acute consume of wine (5 ml/kg body weight), induces nuclear translocation of NF-κB and AP-1 in the absence of any further stimulus. On the other hand, TNF-α treatment in the presence of RWS is associated with a delay in transcription factor activation and to a negative modulation on the expression of specific genes. Moreover, RWS stimulates c-jun binding to the tissue-type plasminogen activator cAMP responsive element consensus site modulating the expression of the specific gene downstream. These results confirm that RW metabolites affect the activity of different transcription factors playing an important preconditioning role in the modulation of the inflammatory pathway in endothelial cells. This is the first report on the effects of a complex food matrix, on the molecular mechanisms associated with inflammatory response in HUVEC cultured in condition that reproduces the physiological environment occurring in vivo.

Scutellarin Mitigates Cancer-Induced Bone Pain by Suppressing CaMKII/CREB Pathway in Rat Models

2019 ◽  
Vol 17 (3) ◽  
pp. 249-253
Author(s):  
Liu Chenglong ◽  
Liu Haihua ◽  
Zhang Fei ◽  
Zheng Jie ◽  
Wei Fang
Keyword(s):  
Protein Kinase ◽  
Bone Pain ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Dependent Protein Kinase ◽  
Response Element ◽  
Protein Kinase Ii ◽  
Element Binding Protein ◽  
Dependent Protein

Cancer-induced bone pain is a severe and complex pain caused by metastases to bone in cancer patients. The aim of this study was to investigate the analgesic effect of scutellarin on cancer-induced bone pain in rat models by intrathecal injection of Walker 256 carcinoma cells. Mechanical allodynia was determined by paw withdrawal threshold in response to mechanical stimulus, and thermal hyperalgesia was indicated by paw withdrawal latency in response to noxious thermal stimulus. The paw withdrawal threshold and paw withdrawal latencies were significantly decreased after inoculation of tumor cells, whereas administration of scutellarin significantly attenuated tumor cell inoculation-induced mechanical and heat hyperalgesia. Tumor cell inoculation-induced tumor growth was also significantly abrogated by scutellarin. Ca2+/calmodulin-dependent protein kinase II is a multifunctional kinase with up-regulated activity in bone pain models. The activation of Ca2+/calmodulin-dependent protein kinase II triggers phosphorylation of cAMP-response element binding protein. Scutellarin significantly reduced the expression of phosphorylated-Ca2+/calmodulin-dependent protein kinase II and phosphorylated-cAMP-response element binding protein in cancer-induced bone pain rats. Collectively, our study demonstrated that scutellarin attenuated tumor cell inoculation-induced bone pain by down-regulating the expression of phosphorylated-Ca2+/calmodulin-dependent protein kinase II and phosphorylated-cAMP-response element binding protein. The suppressive effect of scutellarin on phosphorylated-Ca2+/calmodulin-dependent protein kinase II/phosphorylated-cAMP-response element binding protein activation may serve as a novel therapeutic strategy for CIBP management.

scholarly journals c-Jun N-Terminal Kinase Activation of Activator Protein-1 Underlies Homologous Regulation of the Gonadotropin-Releasing Hormone Receptor Gene in αT3-1 Cells

Endocrinology ◽  
2003 ◽  
Vol 144 (3) ◽  
pp. 839-849 ◽  
Author(s):  
Buffy S. Ellsworth ◽  
Brett R. White ◽  
Ann T. Burns ◽  
Brian D. Cherrington ◽  
Annette M. Otis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Cell Model ◽  
Receptor Gene ◽  
Critical Role ◽  
Dominant Negative ◽  
Activator Protein 1 ◽  
Activator Protein

Reproductive function is dependent on the interaction between GnRH and its cognate receptor found on gonadotrope cells of the anterior pituitary gland. GnRH activation of the GnRH receptor (GnRHR) is a potent stimulus for increased expression of multiple genes including the gene encoding the GnRHR itself. Thus, homologous regulation of the GnRHR is an important mechanism underlying gonadotrope sensitivity to GnRH. Previously, we have found that GnRH induction of GnRHR gene expression in αT3-1 cells is partially mediated by protein kinase C activation of a canonical activator protein-1 (AP-1) element. In contrast, protein kinase A and a cAMP response element-like element have been implicated in mediating the GnRH response of the GnRHR gene using a heterologous cell model (GGH3). Herein we find that selective removal of the canonical AP-1 site leads to a loss of GnRH regulation of the GnRHR promoter in transgenic mice. Thus, an intact AP-1 element is necessary for GnRH responsiveness of the GnRHR gene both in vitro and in vivo. Based on in vitro analyses, GnRH appeared to enhance the interaction of JunD, FosB, and c-Fos at the GnRHR AP-1 element. Although enhanced binding of cFos reflected an increase in gene expression, GnRH appeared to regulate both FosB and JunD at a posttranslational level. Neither overexpression of a constitutively active Raf-kinase nor pharmacological blockade of GnRH-induced ERK activation eliminated the GnRH response of the GnRHR promoter. GnRH responsiveness was, however, lost in αT3-1 cells that stably express a dominant-negative c-Jun N-terminal kinase (JNK) kinase, suggesting a critical role for JNK in mediating GnRH regulation of the GnRHR gene. Consistent with this possibility, we find that the ability of forskolin and membrane-permeable forms of cAMP to inhibit the GnRH response of the GnRHR promoter is associated with a loss of both JNK activation and GnRH-mediated recruitment of the primary AP-1-binding components.

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