AKT activation triggers Rab14-mediated ADAM10 translocation to the cell surface in human aortic endothelial cells.

ABSTRACT: AKT (protein kinase B) activation reduces the harmful effects of advanced glycation end products (AGEs); however, the protective mechanisms remain unknown. In cultured human aortic endothelial cells (HAECs), we investigated how AKT signaling suppresses AGEs-induced intercellular adhesion molecule-1 (ICAM-1) expression. AGEs of bovine serum albumin (AGE-BSA) increased ICAM-1 expression, but this effect was abolished by pretreatment with the AKT activator SC79. SC79 activated AKT1, AKT2, and AKT3, translocated a disintegrin and metalloprotease 10 (ADAM10) to the cell surface, and induced ectodomain shedding of the receptor for AGEs (RAGE). In contrast, GI 254023X-mediated ADAM10 inhibition and siRNA-mediated ADAM10 knockdown both prevented SC79-induced RAGE ectodomain shedding. On the other

SUBMITTER: Baek CH 

PROVIDER: S-EPMC11876668 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature