Spermidine Confers Liver Protection by Enhancing NRF2 Signaling Through a MAP1S-Mediated Noncanonical Mechanism.

ABSTRACT: Spermidine (SPD), a naturally occurring polyamine, has been recognized as a caloric restriction mimetic that confers health benefits, presumably by inducing autophagy. Recent studies have reported that oral administration of SPD protects against liver fibrosis and hepatocarcinogenesis through activation of microtubule associated protein 1S (MAP1S)-mediated autophagy. Nuclear factor (erythroid-derived 2)-like 2 (NRF2) is a transcription factor that mediates cellular protection by maintaining the cell's redox, metabolic, and proteostatic balance. In this study, we demonstrate that SPD is a noncanonical NRF2 inducer, and that MAP1S is a component of this noncanonical pathway of NRF2 activation. Mechanistically, MAP1S induces NRF2 signaling through two parallel mechanisms, both resulting in NR

SUBMITTER: Liu P 

PROVIDER: S-EPMC6597327 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature