Angiotensin converting enzyme 2 in the brain

Angiotensinogen (AGT) produced by glial cells is transformed by renin to form Ang-I, which is then converted by ACE into Ang-II. This octapeptide can be hydrolyzed by ACE2 to form Ang-(1-7) or converted to the heptapepetide Ang-III by aminopeptidase A (APA) and further degraded to Ang-IV by aminopeptidase N (APN). ACE2 also cleaves Ang-I to Ang-(1-9), the latter being converted by ACE into Ang-(1-7). Ang-(1-7) can also be formed by neprilysin (NEP) from Ang-I or Ang-(1-9). ACE metabolizes Ang-(1-7) to the inactive peptide Ang-(1-5). The recently discovered Ang-(1-12) could originate from AGT and potentially generate Ang-II or Ang-(1-7). Ang-II acting on AT1 receptors (AT1R) can activate mitogen-activated protein kinase kinase (MAPKK), leading to enhanced p38 kinase activity, phosphorylation of ERK1/2 and increased expression of c-jun and c-fos. AT1R also ultimately increase reactive oxygen species (ROS) production via NAD(P)H oxidase (not represented here). On the other side AT2R oppose AT1R-mediated signaling. Ang-(1-7) acting on the Mas receptor may attenuate the actions of the ACE/Ang-II/AT1R pathway through inhibition of the MAPKK pathway and stimulation of nitric oxide (NO) release. In addition to Ang-II, renin binding to (Pro)renin receptors (PRR) and Ang-III binding to AT1R also trigger activation of the MAPKK-ERK1/2 signaling pathway. AT4R/IRAP activation induces c-fos expression and probable NO release.

Publication

Angiotensin converting enzyme 2 in the brain. () Huijing Xia, et al. J Neurochem. ;107(6):1482-1494. Figure: F1. All organisms Drosophila melanogaster Homo sapiens

Disease mentions