Characterization of a stellate cell activation-associated protein (STAP) with peroxidase activity found in rat hepatic stellate cells

A proteome approach for the molecular analysis of the activation of rat ste llate cell, a liver-specific pericyte, led to the discovery of a novel prot ein named STAP (stellate cell activation-associated protein). We cloned STA P cDNA, STAP is a cytoplasmic protein with molecular weight of 21,496 and s hows about 40% amino acid sequence homology with myoglobin, STAP was dramat ically induced in in vivo activated stellate cells isolated from fibrotic l iver and in stellate cells undergoing in vitro activation during primary cu lture. This induction was seen together with that of other activation-assoc iated molecules, such as smooth muscle alpha -actin, PDGF receptor-beta, an d neural cell adhesion molecule. The expression of STAP protein and mRNA wa s augmented time dependently in thioacetamide-induced fibrotic liver. Immun oelectron microscopy and proteome analysis detected STAP in stellate cells but not in other hepatic constituent cells. Biochemical characterization of recombinant rat STAP revealed that STAP is a heme protein exhibiting perox idase activity toward hydrogen peroxide and linoleic acid hydroperoxide. Th ese results indicate that STAP is a novel endogenous peroxidase catabolizin g hydrogen peroxide and lipid hydroperoxides, both of which have been repor ted to trigger stellate cell activation and consequently promote progressio n of liver fibrosis, STAP could thus play a role as an antifibrotic scaveng er of peroxides in the liver.