3-ketodihydrosphingosine reductase mutation induces steatosis and hepatic injury in zebrafish.

ABSTRACT: 3-ketodihydrosphingosine reductase (KDSR) is the key enzyme in the de novo sphingolipid synthesis. We identified a novel missense kdsr^I105R mutation in zebrafish that led to a loss of function, and resulted in progression of hepatomegaly to steatosis, then hepatic injury phenotype. Lipidomics analysis of the kdsr^I105R mutant revealed compensatory activation of the sphingolipid salvage pathway, resulting in significant accumulation of sphingolipids including ceramides, sphingosine and sphingosine 1-phosphate (S1P). Ultrastructural analysis revealed swollen mitochondria with cristae damage in the kdsr^I105R mutant hepatocytes, which can be a cause of hepatic injury in the mutant. We found elevated sphingosine kinase 2 (sphk2) expression in the kdsr^I105R</

SUBMITTER: Park KH 

PROVIDER: S-EPMC6361991 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature