scholarly journals Pituitary adenylate cyclase-activating polypeptide acts synergistically with relaxin in modulating ovarian cell function in rats

2000 ◽  
Vol 167 (1) ◽  
pp. 61-69 ◽  
Author(s):  
CH Teng ◽  
FC Ke ◽  
MT Lee ◽  
SW Lin ◽  
L Chen ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Gelatin Zymography ◽  
Interstitial Cells ◽  
Camp Signaling ◽  
Matrix Metalloproteinase 2 ◽  
Ovarian Cells ◽  
Camp Signaling Pathway ◽  
Pituitary Adenylate Cyclase

The interactive effects of pituitary adenylate cyclase-activating polypeptide (PACAP) and relaxin on the secretion of gelatinases, involved in matrix remodeling, in ovarian theca-interstitial cells and granulosa cells, were investigated in gonadotropin-primed immature rats. The gelatinases secreted from cultured cells were analyzed using gelatin zymography and scanning densitometry. We have previously shown that relaxin stimulated the secretion of a 71 kDa gelatinase, identified as a type IV collagenase (matrix metalloproteinase 2), in rat theca-interstitial cells. This study has demonstrated that PACAP27 and PACAP38, with similar potency, dose-dependently enhanced relaxin-induced secretion of 71 kDa gelatinase, whereas PACAP alone had no effect. In rat granulosa cells, both PACAP27 and PACAP38 alone dose-dependently increased the secretion of a 63 kDa gelatinase. In addition, this study has shown that cAMP signaling pathway mediators act similarly to that of PACAP on gelatinase secretion in rat ovarian cells. Cholera toxin, forskolin and 8-bromoadenosine cAMP augmented relaxin-induced secretion of 71 kDa gelatinase in theca-interstitial cells, and alone they had no effect. These mediators also increased the secretion of 63 kDa gelatinase in granulosa cells. It is well known that the increase in cellular cAMP level is associated with the morphological rounding-up phenomenon in granulosa cells. This study has shown that PACAP and cAMP pathway mediators, but not relaxin, could cause such changes in cell shape in granulosa cells as well as in theca-interstitial cells. In conclusion, this study provides original findings that PACAP acts synergistically with relaxin in stimulating the secretion of gelatinases in rat ovarian theca-interstitial cells and granulosa cells. This supports the idea that relaxin and PACAP may serve as ovarian physiological mediators of gonadotropin function in facilitating the ovulatory process. In addition, PACAP appears to act through the cAMP signaling pathway to affect biological functions in ovarian cells, whereas relaxin does not.

Hydroxyurea Induces Fetal Hemoglobin Expression by Activating cAMP Signaling Pathways In a cAMP- and cGMP-Dependent Manner; New Hypothesis to Account for a Role of Non-Erythroid Cells In Fetal Hemoglobin Induction

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1622-1622 ◽  
Author(s):  
Tohru Ikuta ◽  
Diana Gutsaeva ◽  
James Parkerson ◽  
Shobha Yerigenahally ◽  
C. Alvin Head
Keyword(s):  
Adenylate Cyclase ◽  
Signaling Pathway ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Fetal Hemoglobin ◽  
Camp Signaling ◽  
Erythroid Cells ◽  
Camp Signaling Pathway ◽  
Camp And Cgmp ◽  
Cox 1

Abstract Abstract 1622 Despite considerable concerns and efforts, the mechanism of action of hydroxyurea (HU) for the induction of fetal hemoglobin (HbF) remains elusive. For example, clinical studies with HU suggest that bone marrow reserve is critical for HbF response to HU, but the underlying mechanism remains unknown. We and others have demonstrated that HU activates the cGMP signaling pathway in erythroid cells, which plays a role in HbF induction. However, the mechanisms by which intracellular signals are transduced to downstream cascades of cyclic nucleotide-dependent pathways in erythroid cells treated with HU remain to be established. Here we present evidence that HU induces HbF expression by activating the cAMP signaling pathway through two independent mechanisms: cAMP and cGMP. To study signal transduction by HU in cyclic nucleotide-dependent pathways, we initially focused on identifying substrates for cAMP-dependent protein kinase (PKA) and cGMP-dependent protein kinase (PKG) that are expressed in erythroid-lineage cells. We found that vasodilator-stimulated phosphoprotein (VASP), which is a 46/50-kDa phosphoprotein expressed in platelets at high levels, is also expressed in erythroid-lineage cells. VASP can be phosphorylated by cyclic nucleotide-elevating agents such as forskolin (activator of adenylate cyclase) and nitric oxide donors (activator of soluble guanylate cyclase). Interestingly, cAMP and cGMP phosphorylate distinct serine residues of VASP; Ser157 is phosphorylated by cAMP-elevating agents, while cGMP-elevating agents phosphorylated Ser239. Although HU increased both intracellular cAMP and cGMP levels in CD34+-derived erythroblasts, we found that Ser157, but not Ser239, is phosphorylated in adult erythroid cells treated with HU, suggesting activation of the cAMP signaling pathway. However, HU-induced HbF expression was down-regulated by inhibiting the activity of adenylate cyclase or soluble guanylate cyclase, suggesting that both enzymes are involved in HU-induced HbF expression. Our studies found that HU decreased the expression of cGMP-inhibitable phosphodiesterase 3B in a manner dependent on soluble guanylate cyclase, resulting in activation of the cAMP signaling pathway. Although a recent study showed that HU directly activates soluble guanylate cyclase, our studies showed that HU is unable to directly stimulate the enzyme activity of adenylate cyclase. Furthermore, HU induced the expression of cyclooxygenase-1 (COX-1) and increased the production of prostaglandin E2 (PGE2) that activates adenylate cyclase through G protein-coupled E-prostanoid receptors. Plasma PGE2 levels were also elevated in sickle cell patients upon HU therapy. These results demonstrate that HU induces HbF expression by activating the cAMP pathway by cAMP- and cGMP-dependent mechanisms, producing redundancy in the response of HbF to HU. Both cAMP and cGMP may represent major molecules that transduce signals from HU to the fetal globin gene. It is known that non-erythroid cells such as leukocytes and monocytes produce a large amount of PGE2. Thus, the involvement of PGE2 in HU-induced HbF expression may suggest an important role of non-erythroid cells as well as bone marrow reserve in the induction of HbF expression. More interestingly, several single nucleotide polymorphisms with amino acid changes have been demonstrated for COX-1; some genetic variants exhibit reduced COX activities. If SCD patients have some mutations in the COX-1 gene, such patients might be resistant to HU therapy. Disclosures: No relevant conflicts of interest to declare.

Atrazine suppresses FSH-induced steroidogenesis and LH-dependent expression of ovulatory genes through PDE-cAMP signaling pathway in human cumulus granulosa cells

2018 ◽  
Vol 461 ◽  
pp. 79-88 ◽  
Author(s):  
Kristina Pogrmic-Majkic ◽  
Dragana Samardzija ◽  
Natasa Stojkov-Mimic ◽  
Jelena Vukosavljevic ◽  
Aleksandra Trninic-Pjevic ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Granulosa Cells ◽  
Camp Signaling ◽  
Camp Signaling Pathway

Mahuannin B an adenylate cyclase inhibitor attenuates hyperhidrosis via suppressing β 2 -adrenoceptor/cAMP signaling pathway

Phytomedicine ◽  
2017 ◽  
Vol 30 ◽  
pp. 18-27 ◽  
Author(s):  
Zengyong Wang ◽  
Yu Cui ◽  
Guoyu Ding ◽  
Mengge Zhou ◽  
Xiaoyao Ma ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Signaling Pathway ◽  
Camp Signaling ◽  
Camp Signaling Pathway

scholarly journals Role of cAMP in Double Switch of Glucagon Secretion

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 896
Author(s):  
Jan Zmazek ◽  
Vladimir Grubelnik ◽  
Rene Markovič ◽  
Marko Marhl
Keyword(s):  
Glucose Metabolism ◽  
Signaling Pathway ◽  
Cell Model ◽  
Dominant Role ◽  
Glucagon Secretion ◽  
Camp Signaling ◽  
Independent Manner ◽  
Metabolic Switch ◽  
Camp Signaling Pathway ◽  
Double Switch

Glucose metabolism plays a crucial role in modulating glucagon secretion in pancreatic alpha cells. However, the downstream effects of glucose metabolism and the activated signaling pathways influencing glucagon granule exocytosis are still obscure. We developed a computational alpha cell model, implementing metabolic pathways of glucose and free fatty acids (FFA) catabolism and an intrinsically activated cAMP signaling pathway. According to the model predictions, increased catabolic activity is able to suppress the cAMP signaling pathway, reducing exocytosis in a Ca2+-dependent and Ca2+ independent manner. The effect is synergistic to the pathway involving ATP-dependent closure of KATP channels and consequent reduction of Ca2+. We analyze the contribution of each pathway to glucagon secretion and show that both play decisive roles, providing a kind of “secure double switch”. The cAMP-driven signaling switch plays a dominant role, while the ATP-driven metabolic switch is less favored. The ratio is approximately 60:40, according to the most recent experimental evidence.

scholarly journals Assessment of cellular mechanisms contributing to cAMP compartmentalization in pulmonary microvascular endothelial cells

2012 ◽  
Vol 302 (6) ◽  
pp. C839-C852 ◽  
Author(s):  
Wei P. Feinstein ◽  
Bing Zhu ◽  
Silas J. Leavesley ◽  
Sarah L. Sayner ◽  
Thomas C. Rich
Keyword(s):  
Endothelial Cells ◽  
Adenylyl Cyclase ◽  
Signaling Pathway ◽  
Camp Signaling ◽  
Microvascular Endothelial Cells ◽  
Camp Production ◽  
Barrier Integrity ◽  
Pulmonary Microvascular Endothelial Cells ◽  
Camp Signaling Pathway ◽  
Microvascular Endothelial

Cyclic AMP signals encode information required to differentially regulate a wide variety of cellular responses; yet it is not well understood how information is encrypted within these signals. An emerging concept is that compartmentalization underlies specificity within the cAMP signaling pathway. This concept is based on a series of observations indicating that cAMP levels are distinct in different regions of the cell. One such observation is that cAMP production at the plasma membrane increases pulmonary microvascular endothelial barrier integrity, whereas cAMP production in the cytosol disrupts barrier integrity. To better understand how cAMP signals might be compartmentalized, we have developed mathematical models in which cellular geometry as well as total adenylyl cyclase and phosphodiesterase activities were constrained to approximate values measured in pulmonary microvascular endothelial cells. These simulations suggest that the subcellular localizations of adenylyl cyclase and phosphodiesterase activities are by themselves insufficient to generate physiologically relevant cAMP gradients. Thus, the assembly of adenylyl cyclase, phosphodiesterase, and protein kinase A onto protein scaffolds is by itself unlikely to ensure signal specificity. Rather, our simulations suggest that reductions in the effective cAMP diffusion coefficient may facilitate the formation of substantial cAMP gradients. We conclude that reductions in the effective rate of cAMP diffusion due to buffers, structural impediments, and local changes in viscosity greatly facilitate the ability of signaling complexes to impart specificity within the cAMP signaling pathway.

scholarly journals Increased Rho-kinase-mediated prostate contractions associated with impairment of β-adrenergic-cAMP-signaling pathway by chronic nitric oxide deficiency

2015 ◽  
Vol 758 ◽  
pp. 24-30 ◽  
Author(s):  
Fabiano Beraldi Calmasini ◽  
Luiz Osório Silveira Leiria ◽  
Marcos José Alves ◽  
Fernando Ricardo Báu ◽  
Eduardo Costa Alexandre ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Rho Kinase ◽  
Camp Signaling ◽  
Camp Signaling Pathway ◽  
Nitric Oxide Deficiency

ChemInform Abstract: Ansellone A (I), a Sesterterpenoid Isolated from the Nudibranch Cadlina luteromarginata and the Sponge Phorbas sp., Activates the cAMP Signaling Pathway.

ChemInform ◽  
2010 ◽  
Vol 41 (48) ◽  
pp. no-no
Author(s):  
Julie Daoust ◽  
Angelo Fontana ◽  
Catherine E. Merchant ◽  
Nicole J. de Voogd ◽  
Brian O. Patrick ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Camp Signaling ◽  
Camp Signaling Pathway
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