scholarly journals Transcription factors regulated by cAMP in smooth muscle of the myometrium at human parturition

2021 ◽  
Vol 49 (2) ◽  
pp. 997-1011
Author(s):  
Jonathan K.H. Li ◽  
Pei F. Lai ◽  
Rachel M. Tribe ◽  
Mark R. Johnson
Keyword(s):  
Smooth Muscle ◽  
Progesterone Receptors ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cell Types ◽  
Nuclear Factor Κb ◽  
Activator Protein 1 ◽  
Camp Response Element ◽  
Expression Of Genes ◽  
Human Parturition

Cyclic adenosine monophosphate (cAMP) contributes to maintenance of a quiescent (relaxed) state in the myometrium (i.e. uterine smooth muscle) during pregnancy, which most commonly has been attributed to activation of protein kinase A (PKA). PKA-mediated phosphorylation of cytosolic contractile apparatus components in myometrial smooth muscle cells (mSMCs) are known to promote relaxation. Additionally, PKA also regulates nuclear transcription factor (TF) activity to control expression of genes important to the labour process; these are mostly involved in actin-myosin interactions, cell-to-cell connectivity and inflammation, all of which influence mSMC transition from a quiescent to a contractile (pro-labour) phenotype. This review focuses on the evidence that cAMP modulates the activity of TFs linked to pro-labour gene expression, predominantly cAMP response element (CRE) binding TFs, nuclear factor κB (NF-κB), activator protein 1 (AP-1) family and progesterone receptors (PRs). This review also considers the more recently described exchange protein directly activated by cAMP (EPAC) that may oppose the pro-quiescent effects of PKA, as well as explores findings from other cell types that have the potential to be of novel relevance to cAMP action on TF function in the myometrium.

Phosphodiesterase 4 Inhibitor Roflumilast Improves the Bronchodilative Effect of Sevoflurane in Sensitized Airways

2014 ◽  
Vol 120 (5) ◽  
pp. 1152-1159 ◽  
Author(s):  
Jing Zhou ◽  
Sohshi Iwasaki ◽  
Michiaki Yamakage
Keyword(s):  
Smooth Muscle ◽  
Volatile Anesthetic ◽  
Cyclic Adenosine Monophosphate ◽  
Relaxation Effect ◽  
Adenosine Monophosphate ◽  
Bronchodilator Effect ◽  
Phosphodiesterase 4 ◽  
Phosphodiesterase 4 Inhibitors ◽  
Lung Resistance ◽  
Total Lung Resistance

Abstract Background: Although phosphodiesterase 4 inhibitors and the volatile anesthetic sevoflurane are known to have independent bronchodilator properties, the combined administration of these two agents may have the potential to exert an additive or synergistic bronchodilator effect. The authors tested this hypothesis and investigated the common site of this combined relaxation effect in a model of airway hyperresponsiveness with ovalbumin-sensitized guinea pigs. Methods: Ovalbumin-sensitized animals (n = 138) were randomized into six groups: sensitized, sevoflurane, rolipram1.0, roflumilast1.0, sevoflurane/rolipram1.0, and sevoflurane/roflumilast1.0. Total lung resistance in vivo, airway smooth muscle tension in vitro, and intracellular cyclic adenosine monophosphate levels were measured to evaluate the relaxation effect. Results: Among the six sensitized groups, total lung resistance was higher in the order of sensitized > sevoflurane > rolipram 1.0 > roflumilast1.0 > sevoflurane/rolipram1.0 > sevoflurane/roflumilast1.0, with an increase in acetylcholine concentration. Compared with the other five groups, the muscle tensions in the sevoflurane/roflumilast1.0 group were significantly lower at carbacholine doses of 10−7, 10−6, and 10−5 M; the cyclic adenosine monophosphate concentrations (means ± SD) in the sevoflurane/rolipram1.0 (1.61 ± 0.34) and sevoflurane/roflumilast1.0 (1.50 ± 0.20) groups were higher than that in the sensitized (0.52 ± 0.15) and sevoflurane (1.12 ± 0.32) groups. Conclusions: The combined use of phosphodiesterase 4 inhibitors with the volatile anesthetic sevoflurane had an additive bronchodilator effect in ovalbumin-sensitized guinea pigs. The concurrent increase in cyclic adenosine monophosphate levels in sensitized airway smooth muscle might be a mechanism of this combined relaxation effect.

259 PRELIMINARY INVESTIGATIONS OF THE EFFECT OF NITRIC OXIDE ON THE EXPRESSION OF GENES INVOLVED IN THE NITRIC OXIDE/CYCLIC GUANOSINE MONOPHOSPHATE/CYCLIC ADENOSINE MONOPHOSPHATE PATHWAY DURING MEIOSIS RESUMPTION IN BOVINE OOCYTES

2013 ◽  
Vol 25 (1) ◽  
pp. 277
Author(s):  
K. R. L. Schwarz ◽  
M. R. Chiaratti ◽  
L. G. Mesquita ◽  
C. L. V. Leal
Keyword(s):  
Nitric Oxide ◽  
Oocyte Maturation ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Temporary Increase ◽  
Expression Of Genes ◽  
Genes Encoding

Nitric oxide is a chemical messenger generated by the activity of the enzyme NO synthase (NOS) and has been implicated in the control of oocyte maturation. Nitric oxide stimulates guanylate cyclase (GC) to produce cyclic guanosine monophosphate (cGMP), which in turn activates cGMP-dependent protein kinase (PKG) and some phosphodiesterases (PDE) that may interfere with cyclic adenosine monophosphate (cAMP) levels, a nucleotide also involved in meiosis resumption. In a previous study, we found that increasing NO levels in the presence of a NO donor (S-nitroso-N-acetylpenicillamine, SNAP) resulted in a delayed resumption of meiosis and a lower rate of germinal vesicle breakdown after 9 h of in vitro maturation. A temporary increase in cGMP levels was also observed with the same treatment, which was reversed by inhibiting GC activity with oxadiazolo-quinoxaline-one (ODQ; unpublished data). These results suggest that NO acted via GC/cGMP and that even a temporary increase in the cGMP level led to a delay of meiosis resumption. The aim of the present study was to determine the role played by NO on the expression of genes encoding for enzymes of the NO/GC/cGMP and cAMP pathways during the first 9 h of oocyte maturation. Cumulus–oocyte complexes were in vitro matured for 9 h in a semi-defined medium (TCM-199 + 3 mg mL–1 of BSA) with 10 to 7 M SNAP associated or not associated with 100 µM ODQ, a GC inhibitor. A group of oocytes incubated in the absence of inhibitors was considered the control. Total RNA was extracted from pools of 20 denuded oocytes with TRIzol (Life Technologies, Grand Island, NY, USA) and reverse transcribed into complementary DNA using a high-capacity reverse transcription kit (Applied Biosystems, Foster City, CA, USA). Quantitative PCR was performed by real-time PCR using SYBR Green (Applied Biosystems). The genes that had their expression measured pertained to one of the following groups: 1) genes encoding for enzymes that synthesise NO (NOS2 and NOS3); 2) genes involved in the control of cGMP levels (GUCY1B3 and PDE5A) or the enzymes activated by it (PKG1 and PKG2); or 3) genes involved in the control of cAMP levels (ADCY3, ADCY6, ADCY9, PDE3A, and PDE8A) or one of the enzymes activated by it (PKA1). GAPDH and PPIA were selected as housekeeping genes using qbasePLUS version 2.3 (Biogazelle, Zwijnaarde, Belgium). Data from 5 replicates were analysed using LinRegPCR version 11.1 and SAS version 9.2 (SAS Institute Inc., Cary, NC, USA). All genes were found to be expressed in the three experimental groups; however, a significant difference in gene expression levels was not found among groups. Results suggest that NO does not act on oocyte maturation by affecting the expression of the investigated genes in oocytes. To our knowledge, this is the first report to demonstrate the expression of the ADCY3, ADCY6, and ADCY9 genes in bovine oocytes. Further research is in progress to study the effect of the SNAP treatment on the expression of these genes in cumulus cells. Financial support from FAPESP 2010/18023-9.

scholarly journals Rottlerin Reduces cAMP/CREB-Mediated Melanogenesis via Regulation of Autophagy

2019 ◽  
Vol 20 (9) ◽  
pp. 2081 ◽  
Author(s):  
Nurinanda Prisky Qomaladewi ◽  
Mi-Yeon Kim ◽  
Jae Youl Cho
Keyword(s):  
Signaling Pathway ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Camp Response Element Binding ◽  
Sequential Process ◽  
Camp Response Element ◽  
Melanin Production ◽  
Melanocyte Stimulating Hormone ◽  
Cellular Autophagy

Melanogenesis is the sequential process of melanin production by melanocytes in order to protect the skin from harmful stimuli. Melanogenesis is disrupted by radiation exposure, which results in the differentiation of melanocytes into melanoma. Recently, some methods have been developed to maintain the instability of melanogenesis in melanoma by activating cellular autophagy. However, there is still a lack of knowledge about how autophagy is involved in the regulation of melanogenesis in melanoma cells. Here, we used rottlerin as an autophagy inducer to investigate the role of the cyclic adenosine monophosphate (cAMP)/cAMP response element binding (CREB) signaling pathway in melanogenesis. We found that rottlerin can inhibit melanin production by targeting cAMP, which is initially activated by alpha-melanocyte stimulating hormone (α-MSH). Our findings suggest that rottlerin has a pivotal role as an autophagy inducer in the regulation of melanogenesis by targeting the cAMP/CREB signaling pathway.

scholarly journals ILF2 Directly Binds and Stabilizes CREB to Stimulate Malignant Phenotypes of Liver Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Hui Du ◽  
Yun Le ◽  
Fenyong Sun ◽  
Kai Li ◽  
Yanfeng Xu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Liver Cancer Cells ◽  
Binding Factor ◽  
Element Binding Protein

Cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) is overexpressed and has an oncogenic role in hepatocellular carcinoma (HCC). Interleukin enhancer binding factor 2 (ILF2) has become research hotspot in liver cancer recently. However, it is still unclear whether and how CREB and ILF2 interact with each other. And how this interaction exerts its role in occurrence and development of liver cancer is still unclear. Here, we found that ILF2 directly bound with CREB, and this binding was essential for the malignant phenotypes of liver cancer cells. Moreover, we found that ILF2 acted as one of the upstream proteins of CREB and promoted CREB only in the protein level, whereas ILF2 expression was not regulated by CREB. Mechanistically, ILF2 bound to the pKID domain of CREB and stimulated its phosphorylation at Ser133. Taken together, our study finds a novel interaction between CREB and ILF2 in liver cancer, and this interaction might play a role in the diagnosis and remedy of liver cancer.

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