General Information:

Id: 9,686
Diseases: Cardiovascular disease
Mammalia
article
Reference: Jesus ICG et al.(2018) Alamandine acts via MrgD to induce AMPK/NO activation against ANG II hypertrophy in cardiomyocytes Am. J. Physiol. 314: C702-C711 [PMID: 29443552]

Interaction Information:

Comment The renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of cardiovascular diseases. Alamandine and its receptor MrgD are components of RAS. In this study goal was twofold: 1) to unravel the signaling molecules activated by the alamandine/MrgD axis in cardiomyocytes; and 2) to evaluate the ability of this axis to prevent angiotensin II (ANG II)-induced hypertrophy. In cardiomyocytes from C57BL/6 mice, alamandine treatment induced an increase in nitric oxide (NO) production, which was blocked by d-Pro7-ANG-(1-7), a MrgD antagonist. This NO rise correlated with increased phosphorylation of AMPK. Alamandine-induced NO production was preserved in Mas-/- myocytes and lost in MrgD-/- cells. Binding of fluorescent-labeled alamandine was observed in wild-type cells, but it was dramatically reduced in MrgD-/- myocytes.
Formal Description
Interaction-ID: 102208

gene/protein

Alamandine

increases_quantity of

drug/chemical compound

NO

in ventricular cardiomyocytes
Comment The renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of cardiovascular diseases. Alamandine and its receptor MrgD are components of RAS. In this study goal was twofold: 1) to unravel the signaling molecules activated by the alamandine/MrgD axis in cardiomyocytes; and 2) to evaluate the ability of this axis to prevent angiotensin II (ANG II)-induced hypertrophy. In cardiomyocytes from C57BL/6 mice, alamandine treatment induced an increase in nitric oxide (NO) production, which was blocked by d-Pro7-ANG-(1-7), a MrgD antagonist. This NO rise correlated with increased phosphorylation of AMPK. Alamandine-induced NO production was preserved in Mas-/- myocytes and lost in MrgD-/- cells. Binding of fluorescent-labeled alamandine was observed in wild-type cells, but it was dramatically reduced in MrgD-/- myocytes.
Formal Description
Interaction-ID: 102330

gene/protein

Alamandine

increases_activity of

complex/PPI

AMPK

in ventricular cardiomyocytes
Comment The renin-angiotensin system (RAS) plays a pivotal role in the pathogenesis of cardiovascular diseases. Alamandine and its receptor MrgD are components of RAS. In this study goal was twofold: 1) to unravel the signaling molecules activated by the alamandine/MrgD axis in cardiomyocytes; and 2) to evaluate the ability of this axis to prevent angiotensin II (ANG II)-induced hypertrophy. Confirming previous data, ANG-(1–7) induced a significant rise in NO.
Formal Description
Interaction-ID: 102331

gene/protein

Angiotensin (1-7)

increases_quantity of

drug/chemical compound

NO

in ventricular cardiomyocytes
Comment To further investigate the signaling pathways involved in the alamandine-induced NO rise, phosphorylation of protein kinase B (Akt), a key protein involved in NO production by ANG-(1–7) was assessed. Acute alamandine treatment for 5 or 15 min had no effect on the phosphorylation of Akt on Ser473, while ANG-(1–7) significantly increased Akt Ser473 phosphorylation.
Formal Description
Interaction-ID: 102332

gene/protein

Alamandine

NOT affects_phosphorylation of

gene/protein

AKT1

at Ser473
Drugbank entries Show/Hide entries for AKT1
Comment To further investigate the signaling pathways involved in the alamandine-induced NO rise, phosphorylation of protein kinase B (Akt), a key protein involved in NO production by ANG-(1–7) was assessed. Acute alamandine treatment for 5 or 15 min had no effect on the phosphorylation of Akt on Ser473, while ANG-(1–7) significantly increased Akt Ser473 phosphorylation.
Formal Description
Interaction-ID: 102333

gene/protein

Angiotensin (1-7)

increases_phosphorylation of

gene/protein

AKT1

at Ser473
Drugbank entries Show/Hide entries for AKT1
Comment MrgD receptors are required for alamandine binding and activation of AMPK/NO signaling in ventricular myocytes.
Formal Description
Interaction-ID: 102334

gene/protein

Alamandine

increases_activity of

gene/protein

MRGPRD

Comment Concomitant incubation with alamandine significantly prevented ANG II-induced cardiomyocyte hypertrophy, indicating that alamandine exerts antihypertrophic effects against ANG II. Corroborating this finding, alamandine treatment also prevented ANG II-induced Myh7 and L-type Ca2+ channel mRNA upregulation.
Formal Description
Interaction-ID: 102335

gene/protein

Alamandine

decreases_activity of

Comment In neonatal rat cardiomyocytes concomitant incubation with alamandine significantly prevented ANG II-induced cardiomyocyte hypertrophy, indicating that alamandine exerts antihypertrophic effects against ANG II. Corroborating this finding, alamandine treatment also prevented ANG II-induced Myh7 and L-type Ca2+ channel mRNA upregulation.
Formal Description
Interaction-ID: 102336

gene/protein

Alamandine

affects_expression of

gene/protein

MYH7

Drugbank entries Show/Hide entries for MYH7
Comment In neonatal rat cardiomyocytes concomitant incubation with alamandine significantly prevented ANG II-induced cardiomyocyte hypertrophy, indicating that alamandine exerts antihypertrophic effects against ANG II. Corroborating this finding, alamandine treatment also prevented ANG II-induced Myh7 and L-type Ca2+ channel mRNA upregulation.
Formal Description
Interaction-ID: 102337

gene/protein

Alamandine

affects_activity of

complex/PPI

Voltage-gated calcium channel, L-type