Nrf2 activation attenuates genetic endoplasmic reticulum stress induced by a mutation in the phosphomannomutase 2 gene in zebrafish.

ABSTRACT: Nrf2 plays critical roles in animals' defense against electrophiles and oxidative stress by orchestrating the induction of cytoprotective genes. We previously isolated the zebrafish mutant it768, which displays up-regulated expression of Nrf2 target genes in an uninduced state. In this paper, we determine that the gene responsible for it768 was the zebrafish homolog of phosphomannomutase 2 (Pmm2), which is a key enzyme in the initial steps of N-glycosylation, and its mutation in humans leads to PMM2-CDG (congenital disorders of glycosylation), the most frequent type of CDG. The pmm2^it768 larvae exhibited mild defects in N-glycosylation, indicating that the pmm2^it768 mutation is a hypomorph, as in human PMM2-CDG patients. A gen

SUBMITTER: Mukaigasa K 

PROVIDER: S-EPMC5856520 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature