PERSONAL DE APOYO
MUÑOZ marina Cecilia
artículos
Título:
Angiotensin-(1-7) stimulates the phosphorylation of JAK2, IRS-1 and Akt in rat heart in vivo: Role of the AT1 and Mas receptors
Autor/es:
JORGE F GIANI; MARIELA M GIRONACCI; MARINA C MUÑOZ; CLARA PEÑA; DANIEL TURYN; FERNANDO P DOMINICI
Revista:
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Editorial:
The American Physiological Society
Referencias:
Lugar: Bethesda, Maryland, EEUU; Año: 2007 vol. 293 p. 1154 - 1163
ISSN:
0363-6135
Resumen:
Angiotensin (ANG) II exerts a negative modulation on insulin signal transduction that might be involved in the pathogenesis of hypertension and insulin resistance. ANG-(17), an endogenous heptapeptide hormone formed by cleavage of ANG I and ANG II, counteracts many actions of ANG II. In the current study, we have explored the role of ANG-(17) in the signaling crosstalk that exists between ANG II and insulin. We demonstrated that ANG-(17) stimulates the phosphorylation of Janus kinase 2 (JAK2) and insulin receptor substrate (IRS)-1 in rat heart in vivo. This stimulating effect was blocked by administration of the selective ANG type 1 (AT1) receptor blocker losartan. In contrast to ANG II, ANG-(17) stimulated cardiac Akt phosphorylation, and this stimulation was blunted in presence of the receptor Mas antagonist A-779 or the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin. The specific JAK2 inhibitor AG-490 blocked ANG-(17)-induced JAK2 and IRS-1 phosphorylation but had no effect on ANG-(17)-induced phosphorylation of Akt, indicating that activation of cardiac Akt by ANG-(17) appears not to involve the recruitment of JAK2 but proceeds through the receptor Mas and involves PI3K. Acute in vivo insulin-induced cardiac Akt phosphorylation was inhibited by ANG II. Interestingly, coadministration of insulin with an equimolar mixture of ANG II and ANG-(17) reverted this inhibitory effect. On the basis of our present results, we postulate that ANG-(17) could be a positive physiological contributor to the actions of insulin in heart and that the balance between ANG II and ANG-(17) could be relevant for the association among insulin resistance, hypertension, and cardiovascular disease.
angiotensin II; Janus kinase; insulin receptor substrate-1; signal transduction