Embryonic alcohol exposure disrupts the ubiquitin-proteasome system.

ABSTRACT: Ethanol (EtOH) is a commonly encountered teratogen that can disrupt organ development and lead to fetal alcohol spectrum disorders (FASDs); many mechanisms of developmental toxicity are unknown. Here, we used transcriptomic analysis in an established zebrafish model of embryonic alcohol exposure (EAE) to identify the ubiquitin-proteasome system (UPS) as a critical target of EtOH during development. Surprisingly, EAE alters 20S, 19S, and 11S proteasome gene expression and increases ubiquitylated protein load. EtOH and its metabolite acetaldehyde decrease proteasomal peptidase activity in a cell type-specific manner. Proteasome 20S subunit β 1 (psmb1hi2939Tg) and proteasome 26S subunit, ATPase 6 (psmc6hi3593Tg), genetic KOs define the developmental impact of decreased proteasome function. Im

SUBMITTER: Weeks O 

PROVIDER: S-EPMC9746913 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature