scholarly journals 20-Hydroxyecdysone activates the protective arm of the renin angiotensin system via Mas receptor

2020 ◽  
Author(s):  
René Lafont ◽  
Sophie Raynal ◽  
Maria Serova ◽  
Blaise Didry-Barca ◽  
Louis Guibout ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mechanism Of Action ◽  
Muscle Growth ◽  
Renin Angiotensin System ◽  
Negative Regulator ◽  
Pharmacological Effects ◽  
Reporter System ◽  
Myostatin Gene ◽  
Renin Angiotensin ◽  
Mas Receptor

ABSTRACT20-Hydroxyecdysone (20E) is a steroid hormone that plays a key role in insect development through nuclear ecdysone receptors (EcRs) and at least one membrane GPCR receptor (DopEcR) and displays numerous pharmacological effects in mammals. However, its mechanism of action is still debated, involving either an unidentified GPCR or the estrogen ERβ receptor. The goal of our study was to better understand 20E mechanism of action.A mouse myoblast cell line (C2C12) and the gene expression of myostatin (a negative regulator of muscle growth) was used as a reporter system of anabolic activity. Experiments using protein-bound 20E established the involvement of a membrane receptor. 20E-like effects were also observed with Angiotensin-(1-7), the endogenous ligand of Mas. Additionally, the effect on myostatin gene expression was abolished by Mas receptor knock-down using small interfering RNA (siRNA) or pharmacological inhibitors.17β-Estradiol (E2) also inhibited myostatin gene expression, but protein-bound E2 was inactive, and E2 activity was not abolished by angiotensin-(1-7) antagonists. A mechanism involving cooperation between Mas receptor and a membrane-bound palmitoylated estrogen receptor is proposed.The possibility to activate the Mas receptor with a safe steroid molecule is consistent with the pleiotropic pharmacological effects of ecdysteroids in mammals and indeed this mechanism may explain the close similarity between angiotensin-(1-7) and 20E effects. Our findings open a lot of possible therapeutic developments by stimulating the protective arm of the renin-angiotensin-aldosterone system (RAAS) with 20E.

20-Hydroxyecdysone activates the protective arm of the RAAS via Mas receptor

2021 ◽  
Author(s):  
René Lafont ◽  
Maria Serova ◽  
Blaise Didry-Barca ◽  
Sophie Raynal ◽  
Louis Guibout ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mechanism Of Action ◽  
Muscle Growth ◽  
Negative Regulator ◽  
Pharmacological Effects ◽  
Reporter System ◽  
Myostatin Gene ◽  
Mas Receptor ◽  
Myoblast Cell Line ◽  
Myoblast Cell

20-Hydroxyecdysone (20E) is a steroid hormone that plays a key role in insect development through nuclear ecdysteroid receptors (EcR/RXR complex) and at least one membrane GPCR receptor (DopEcR). It also displays numerous pharmacological effects in mammals, where its mechanism of action is still debated, involving either an unidentified GPCR or the estrogen ERβ receptor. The goal of this study was to better understand 20E mechanism of action in mammals. A mouse myoblast cell line (C2C12) and the gene expression of myostatin (a negative regulator of muscle growth) was used as a reporter system of anabolic activity. Experiments using protein-bound 20E established the involvement of a membrane receptor. 20E-like effects were also observed with angiotensin-(1-7), the endogenous ligand of Mas. Additionally, the effect on myostatin gene expression was abolished by Mas receptor knock-down using small interfering RNA (siRNA) or pharmacological inhibitors. 17β-Estradiol (E2) also inhibited myostatin gene expression, but protein-bound E2 was inactive, and E2 activity was not abolished by angiotensin-(1-7) antagonists. A mechanism involving cooperation between the Mas receptor and a membrane-bound palmitoylated estrogen receptor is proposed. The possibility to activate the Mas receptor with a safe steroid molecule is consistent with the pleiotropic pharmacological effects of ecdysteroids in mammals and, indeed, the proposed mechanism may explain the close similarity between angiotensin-(1-7)’s and 20E’s effects. Our findings open up many possible therapeutic developments involving stimulation of the protective arm of the renin-angiotensin-aldosterone system (RAAS) with 20E.

Physical Exercise and ACE2-Angiotensin-(1-7)-Mas Receptor Axis of the Renin Angiotensin System

2017 ◽  
Vol 24 (9) ◽  
Author(s):  
Albena Nunes-Silva ◽  
Guilherme Carvalho Rocha ◽  
Daniel Massote Magalhaes ◽  
Lucas Neves Vaz ◽  
Marcelo Henrique Salviano de Faria ◽  
...  
Keyword(s):  
Physical Exercise ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Mas Receptor

scholarly journals Alternative renin-angiotensin system pathways in adipose tissue and their role in the pathogenesis of obesity

2016 ◽  
Vol 50 (4) ◽  
pp. 229-240 ◽  
Author(s):  
M Slamkova ◽  
S Zorad ◽  
K Krskova
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Alternative Pathways ◽  
Metabolism Regulation ◽  
Mas Receptor ◽  
Glucose And Lipid Metabolism

AbstractAdipose tissue expresses all the renin-angiotensin system (RAS) components that play an important role in the adipogenesis, lipid and glucose metabolism regulation in an auto/paracrine manner. The classical RAS has been found to be over-activated during the adipose tissue enlargement, thus elevated generation of angiotensin II (Ang II) may contribute to the obesity pathogenesis. The contemporary view on the RAS has become more complex with the discovery of alternative pathways, including angiotensin-converting enzyme 2 (ACE2)/angiotensin (Ang)-(1-7)/Mas receptor, (pro)renin receptor, as well as angiotensin IV(Ang IV)/AT4 receptor. Ang-(1-7) via Mas receptor counteracts with most of the deleterious effects of the Ang II-mediated by AT1 receptor implying its beneficial role in the glucose and lipid metabolism, oxidative stress, inflammation, and insulin resistance. Pro(renin) receptor may play a role (at least partial) in the pathogenesis of the obesity by increasing the local production of Ang II in adipose tissue as well as triggering signal transduction independently of Ang II. In this review, modulation of alternative RAS pathways in adipose tissue during obesity is discussed and the involvement of Ang-(1-7), (pro)renin and AT4 receptors in the regulation of adipose tissue homeostasis and insulin resistance is summarized.

The Renin-Angiotensin System and the Cerebrovascular Diseases: Experimental and Clinical Evidence

2020 ◽  
Vol 27 (6) ◽  
pp. 463-475 ◽  
Author(s):  
Lucas M. Kangussu ◽  
Lucas Alexandre Santos Marzano ◽  
Cássio Ferraz Souza ◽  
Carolina Couy Dantas ◽  
Aline Silva Miranda ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Renin Angiotensin System ◽  
Cerebrovascular Diseases ◽  
Therapeutic Effects ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Mas Receptor

Cerebrovascular Diseases (CVD) comprise a wide spectrum of disorders, all sharing an acquired or inherited alteration of the cerebral vasculature. CVD have been associated with important changes in systemic and tissue Renin-Angiotensin System (RAS). The aim of this review was to summarize and to discuss recent findings related to the modulation of RAS components in CVD. The role of RAS axes is more extensively studied in experimentally induced stroke. By means of AT1 receptors in the brain, Ang II hampers cerebral blood flow and causes tissue ischemia, inflammation, oxidative stress, cell damage and apoptosis. On the other hand, Ang-(1-7) by stimulating Mas receptor promotes angiogenesis in brain tissue, decreases oxidative stress, neuroinflammation, and improves cognition, cerebral blood flow, neuronal survival, learning and memory. In regard to clinical studies, treatment with Angiotensin Converting Enzyme (ACE) inhibitors and AT1 receptor antagonists exerts preventive and therapeutic effects on stroke. Besides stroke, studies support a similar role of RAS molecules also in traumatic brain injury and cerebral aneurysm. The literature supports a beneficial role for the alternative RAS axis in CVD. Further studies are necessary to investigate the therapeutic potential of ACE2 activators and/or Mas receptor agonists in patients with CVD.

Regulation of nonclassical renin-angiotensin system receptor gene expression in the adrenal medulla by acute and repeated immobilization stress

2015 ◽  
Vol 308 (6) ◽  
pp. R517-R529 ◽  
Author(s):  
Regina Nostramo ◽  
Lidia Serova ◽  
Marcela Laukova ◽  
Andrej Tillinger ◽  
Chandana Peddu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adrenal Medulla ◽  
Immobilization Stress ◽  
Receptor Gene ◽  
Renin Angiotensin System ◽  
Mrna Levels ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Catecholamine Biosynthesis ◽  
Receptor Mrna

The involvement of the nonclassical renin-angiotensin system (RAS) in the adrenomedullary response to stress is unclear. Therefore, we examined basal and immobilization stress (IMO)-triggered changes in gene expression of the classical and nonclassical RAS receptors in the rat adrenal medulla, specifically the angiotensin II type 2 (AT2) and type 4 (AT4) receptors, (pro)renin receptor [(P)RR], and Mas receptor (MasR). All RAS receptors were identified, with AT2 receptor mRNA levels being the most abundant, followed by the (P)RR, AT1A receptor, AT4 receptor, and MasR. Following a single IMO, AT2 and AT4 receptor mRNA levels decreased by 90 and 50%, respectively. Their mRNA levels were also transiently decreased by repeated IMO. MasR mRNA levels displayed a 75% transient decrease as well. Conversely, (P)RR mRNA levels were increased by 50% following single or repeated IMO. Because of its abundance, the function of the (P)RR was explored in PC-12 cells. Prorenin activation of the (P)RR increased phosphorylation of extracellular signal-regulated kinase 1/2 and tyrosine hydroxylase at Ser31, likely increasing its enzymatic activity and catecholamine biosynthesis. Together, the broad and dynamic changes in gene expression of the nonclassical RAS receptors implicate their role in the intricate response of the adrenomedullary catecholaminergic system to stress.

scholarly journals 729-1 Modulation of Cardiac Hypertrophy by Blockade of the Renin Angiotensin System: Effects on LVH Regression, Gene Expression, and Survival

1995 ◽  
Vol 25 (2) ◽  
pp. 135A
Author(s):  
Heribert Schunkert ◽  
Günter Bruckschlegel ◽  
Stephan R. Holmer ◽  
Daniela Grimm ◽  
Eckhard P. Kromer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Hypertrophy ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin
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