Ser9 phosphorylation of GSK-3β promotes aging in the heart through suppression of autophagy.

ABSTRACT: Glycogen synthase kinase-3β (GSK-3β) is a serine/threonine kinase and a negative regulator of cardiac hypertrophy. Phosphorylation of GSK-3β at Ser9 negatively regulates its kinase activity. The role of GSK-3β in cardiac aging remains poorly understood. The study aimed to elucidate the role of GSK-3β Ser9 phosphorylation in mediating cardiac aging and the underlying mechanism. Phosphorylation of GSK-3β at Ser9 and the levels of β-catenin and Mcl-1 were increased in the mouse heart during aging, suggesting that GSK-3β is inactivated during aging in the heart. Age-induced cardiac hypertrophy, fibrosis, left ventricular dysfunction, and increases in cardiomyocyte apoptosis and senescence were all attenuated in constitutively active GSK-3βS9A knock-in (KI) mice compared to littermate wild type

SUBMITTER: Chen Y 

PROVIDER: S-EPMC8589323 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature