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 stellate cell, a liver-specific pericyte, led to the discovery of a novel protein named STAP (stellate cell activation-associated protein). We cloned STAP cDNA. STAP is a cytoplasmic protein with molecular weight of 21,496 and shows about 40% amino acid sequence homology with myoglobin. STAP was dramatically induced in in vivo activated stellate cells isolated from fibrotic liver and in stellate cells undergoing in vitro activation during primary culture. This induction was seen together with that of other activation-associated molecules, such as smooth muscle alpha-actin, PDGF receptor-beta, and neural cell adhesion molecule. The expression of STAP protein and mRNA was augmented time dependently in thioacetamide-induced fibrotic liver. Immunoelectron 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 peroxidase activity toward hydrogen peroxide and linoleic acid hydroperoxide. These results indicate that STAP is a novel endogenous peroxidase catabolizing hydrogen peroxide and lipid hydroperoxides, both of which have been reported to trigger stellate cell activation and consequently promote progression of liver fibrosis. STAP could thus play a role as an antifibrotic scavenger of peroxides in the liver.
Kawada
N
N
Department of Hepatology, Graduate School of Medicine, Osaka City University Medical School, Osaka 545-8585, Japan.
Kristensen
D B
DB
Asahina
K
K
Nakatani
K
K
Minamiyama
Y
Y
Seki
S
S
Yoshizato
K
K
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D000078842:Cytoglobin; D018076:DNA, Complementary / Q000737:chemistry; D015180:Electrophoresis, Gel, Two-Dimensional; D004790:Enzyme Induction; D006861:Hydrogen Peroxide / Q000378:metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008103:Liver Cirrhosis / Q000201:enzymology; D008297:Male; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D009195:Peroxidase / Q000378:metabolism*; D010544:Peroxidases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
C000627268:Cygb protein, rat; D000078842:Cytoglobin; D018076:DNA, Complementary; D008054:Lipid Peroxides; D012333:RNA, Messenger; D006861:Hydrogen Peroxide; D010544:Peroxidases; D009195:Peroxidase