Characterization of signaling pathways of Angiotensin I‐Converting Enzyme in mesangial cells of spontaneously hypertensive rats (SHR)

Abstract

Angiotensin I converting enzyme (ACE) is a glycoprotein composed of a single large polypeptide chain, containing two homologous domains, called N- and C-domains, each one with a catalytic site. Recently, signaling pathways triggered by this enzyme have been reported in endothelial cells, showing a new possible role as a transducer molecule. Aiming to explore this hypothesis, we analyzed the activation of JNK and ERK1/2 intracellular signaling pathways after stimulation of CHO cells stably expressing ACE (CHO-ACE) with angiotensin I (AngI, 10-6 M) in the presence and absence of captopril (10-6 M) during different times. Our results show that AngI is able to trigger both signaling pathways activation, and that captopril is unable to impair it. We also performed the same experimental procedure in mesangial cells collected from SHR and Wistar rats. Surprisingly, ERK1/2 activation in mesangial cells from SHR was significantly higher as compared to those from Wistar rats. In summary, our results evidence that ACE is able to activate JNK and ERK 1/2 signaling pathways in both a heterologous (ACE-transfected CHO cells) and endogenous (mesangial cells). Besides that, the higher response found for ERK1/2 in mesangial cells from SHR may shed some light in the signaling pathways regulated by ACE and its possible correlation with hypertension and associated pathological states.