Globotriaosylsphingosine induces oxidative DNA damage in cultured kidney cells
Fabry disease (FD, OMIM 301500) is a genetic disorder caused by deficient/absent activity of the lysosomal enzyme α‐galactosidase A (EC126.96.36.199). Consequently, enzyme substrates – glycosphingolipids (as globotriaosylceramide – Gb3) – progressively accumulate in lysosomes of various cell types and body fluids. Fabry patients present as main pathological features vascular complications, including chronic kidney disease.1 Although it is known that tissue injury is directly related to substrates deposition1 the molecular mechanisms by which it occurs are not completely understood.
Considering that studies have pointed oxidative stress as an important factor on FD pathophysiology3 and globotriaosylsphingosine (lyso‐Gb3) as a potential active metabolite,5 the aim of this study was to investigate the in vitro effects of lyso‐Gb3 on cultured human embryonic kidney cells (HEK‐293 T) concerning to DNA damage and oxidative DNA damage in purines and pyrimidines.