Cytoprotective effects of adrenomedullin in glomerular cell injury: Central role of cAMP signaling pathway

ABSTRACTThe last decade has seen a shift in the theoretical framework addressing the pathophysiology of psychiatric disorders. During this period, research endeavors have been directed toward investigating the biochemical mechanisms involved in the transduction of information from the cell surface to the cell interior. The emerging picture, supported by growing evidence, is that in addition to neurotransmitters and their receptors, various signal transduction pathways may be linked to the pathophysiology of major psychiatric disorders. In this review, the role of one such pathway—the cyclic adenosine monophosphate (cAMP) signaling pathway—will be highlighted. We review data suggesting the involvement of the upstream and downstream components of this system in the pathophysiology of psychiatric disorders.

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Tanshinone IIA Stimulates Cystathionine γ-Lyase Expression and Protects Endothelial Cells from Oxidative Injury

Antioxidants ◽

10.3390/antiox10071007 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1007

Author(s):

Qiaojian Yan ◽

Zhimin Mao ◽

Jingru Hong ◽

Kun Gao ◽

Manabu Niimi ◽

...

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Cell Injury ◽

Tanshinone Iia ◽

Camp Signaling ◽

Endothelial Cell Injury ◽

Creb Phosphorylation ◽

Camp Signaling Pathway ◽

Injury Model

Tanshinone IIA (Tan IIA), an active ingredient of Danshen, is a well-used drug to treat cardiovascular diseases. Currently, the mechanisms involved remain poorly understood. Given that many actions of Tan IIA could be similarly achieved by hydrogen sulfide (H2S), we speculated that Tan IIA might work through the induction of endogenous H2S. This study was to test this hypothesis. Exposure to endothelial cells to Tan IIA elevated H2S-synthesizing enzyme cystathionine γ-Lyase (CSE), associated with an increased level of endogenous H2S and free thiol activity. Further analysis revealed that this effect of Tan IIA was mediated by an estrogen receptor (ER) and cAMP signaling pathway. It stimulated VASP and CREB phosphorylation. Inhibition of ER or PKA abolished the CSE-elevating effect, whereas activation of ER or PKA mimicked the effect of Tan IIA. In an oxidative endothelial cell injury model, Tan IIA potently attenuated oxidative stress and inhibited cell death. In support of a role of endogenous H2S, inhibition of CSE aggerated oxidative cell injury. On the contrary, supplement of H2S attenuated cell injury. Collectively, our study characterized endogenous H2S as a novel mediator underlying the pharmacological actions of Tan IIA. Given the multifaceted functions of H2S, the H2S-stimulating property of Tan IIA could be exploited for treating many diseases.

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Role of α-MSH-MC1R-cAMP Signaling Pathway in Regulating the Melanin Synthesis in Silky Fowl

Journal of Cell Signaling ◽

10.4172/2576-1471.1000195 ◽

2018 ◽

Vol 03 (04) ◽

Author(s):

Guanhong Li ◽

Lanjiao Xu ◽

Miao Xiong ◽

Mingren Qu

Keyword(s):

Signaling Pathway ◽

Camp Signaling ◽

Melanin Synthesis ◽

Camp Signaling Pathway

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cAMP-signaling pathway acts in selective synergism with glucose or tolbutamide to increase cytosolic Ca2+ in rat pancreatic beta-cells

Diabetes ◽

10.2337/diabetes.45.3.295 ◽

1996 ◽

Vol 45 (3) ◽

pp. 295-301 ◽

Cited By ~ 8

Author(s):

K. Yaekura ◽

M. Kakei ◽

T. Yada

Keyword(s):

Signaling Pathway ◽

Beta Cells ◽

Pancreatic Beta Cells ◽

Camp Signaling ◽

Camp Signaling Pathway

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Role of cAMP in Double Switch of Glucagon Secretion

Cells ◽

10.3390/cells10040896 ◽

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.

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

AJP Cell Physiology ◽

10.1152/ajpcell.00361.2011 ◽

2012 ◽

Vol 302 (6) ◽

pp. C839-C852 ◽

Cited By ~ 38

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.

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