ADAM10 metalloprotease is required for activation of Notch-1, a transmembrane receptor regulating cell differentiation, proliferation and apoptosis, whose intracellular proteolytic fragment NICD mediates some key cardiovascular effects of the hormone relaxin (RLX). This study demonstrates the involvement of ADAM10 and PI3K/Akt signaling in mediating RLX-induced Notch-1 activation. H9c2 cardiomyocytes and NIH3T3 fibroblasts were incubated with human RLX-2 (17 nmol/l, 24 h) in presence or absence of the PI3K or Akt inhibitors wortmannin (WT, 100 nmol/l) and triciribine (TCN, 1 μmol/l). Cyclohexanedione-inactivated RLX (iRLX) served as negative control. RLX significantly increased Akt phosphorylation, ADAM10 and NICD expression, which were abolished by WT or TCN and did not occur with iRLX. These findings highlight a new receptor-specific signal transduction pathway of RLX.

Relaxin induces up-regulation of ADAM10 metalloprotease in RXFP1-expressing cells by PI3K/AKT signaling / Boccalini, Giulia; Sassoli, Chiara; Bani, Daniele; Nistri, Silvia. - In: MOLECULAR AND CELLULAR ENDOCRINOLOGY. - ISSN 0303-7207. - STAMPA. - 472:(2018), pp. 80-86. [10.1016/j.mce.2017.11.021]

Relaxin induces up-regulation of ADAM10 metalloprotease in RXFP1-expressing cells by PI3K/AKT signaling

Boccalini Giulia
Membro del Collaboration Group
;
Sassoli Chiara
Membro del Collaboration Group
;
Bani Daniele
Membro del Collaboration Group
;
Nistri Silvia
2018

Abstract

ADAM10 metalloprotease is required for activation of Notch-1, a transmembrane receptor regulating cell differentiation, proliferation and apoptosis, whose intracellular proteolytic fragment NICD mediates some key cardiovascular effects of the hormone relaxin (RLX). This study demonstrates the involvement of ADAM10 and PI3K/Akt signaling in mediating RLX-induced Notch-1 activation. H9c2 cardiomyocytes and NIH3T3 fibroblasts were incubated with human RLX-2 (17 nmol/l, 24 h) in presence or absence of the PI3K or Akt inhibitors wortmannin (WT, 100 nmol/l) and triciribine (TCN, 1 μmol/l). Cyclohexanedione-inactivated RLX (iRLX) served as negative control. RLX significantly increased Akt phosphorylation, ADAM10 and NICD expression, which were abolished by WT or TCN and did not occur with iRLX. These findings highlight a new receptor-specific signal transduction pathway of RLX.
2018
472
80
86
Goal 3: Good health and well-being for people
Boccalini, Giulia; Sassoli, Chiara; Bani, Daniele; Nistri, Silvia
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1107122
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