Molecular and cellular mechanism of angiotensin II-mediated apoptosis.

Published

Journal Article

It is well known that angiotensin II exerts growth promoting effects via the angiotensin II type 1 (AT1) receptor. We have cloned a second type of angiotensin II receptor (AT2 receptor) and demonstrated that this receptor acts as an antagonistic receptor against the AT1 receptor. Moreover, we have demonstrated that the AT2 receptor exerts growth inhibitory and proapoptotic effects by antagonizing the effects of the AT1 receptor and growth factors in several cell lines including vascular smooth muscle cells, cardiomyocytes, neuronal cell (PC12W) and fibroblasts (R3T3). We observed that the AT2 receptor activates tyrosine phosphatase(s) such as mitogen-activated protein (MAP) kinase-phosphatase-1 (MKP-1) and inactivates MAP kinase (extracellular signal-regulated kinase (ERK1 and ERK2)), resulting in Bcl-2 dephosphorylation and up-regulation of Bax. This inactivation of ERK is mediated via Gi protein coupling through its unique intracellular third loop. Moreover, we have demonstrated that interferon regulatory factor (IRF)-1 also up-regulates the AT2 receptor in apoptotic cells, suggesting that the cytokines may play an important role in angiotensin-regulated apoptosis.

Full Text

Duke Authors

Cited Authors

  • Horiuchi, M; Akishita, M; Dzau, VJ

Published Date

  • August 1998

Published In

Volume / Issue

  • 24 / 3-4

Start / End Page

  • 307 - 314

PubMed ID

  • 9888502

Pubmed Central ID

  • 9888502

Electronic International Standard Serial Number (EISSN)

  • 1532-4206

International Standard Serial Number (ISSN)

  • 0743-5800

Digital Object Identifier (DOI)

  • 10.3109/07435809809032610

Language

  • eng