Spermine oxidase promotes oxidative stress during islet inflammation

Metabolomic profiling of zebrafish embryos showed that smox deficiency did not affect spermine or spermidine levels but led to the accumulation of acetylated polyamines, consistent with the rerouting of polyamine flux through alternative acetylation pathways to ensure homeostasis of polyamine levels. RNA sequencing of zebrafish embryos demonstrated that smox deficiency induces distinct transcriptional programs, with enrichment of cell cycle and RNA processing pathways at baseline and reprogramming of stress, translational, and immune-associated pathways during injury.

Mechanistically, Smox generates both hydrogen peroxide and the reactive aldehyde acrolein, whereas Paox-dependent pathways produce hydrogen peroxide without acrolein. These findings support a model in which Smox amplifies β-cell stress through aldehyde-mediated toxicity and identify polyamine catabolism as a modifiable pathway in the setting of β-cell injury.