Characterization of membrane-associated prothrombin activator in normal and injured murine tissues.
Thrombin is a multifunctional enzyme involved in coagulation, cell modulation and inflammation. We recently reported a novel membrane-associated prothrombin activator, abbreviated as MAPA, found in cultured fibroblasts and glial cell lines. In this study, we examined the physiological role of this enzyme. MAPA-like activity was detected in the liver, kidney, lung and heart but not in the spleen or brain in normal mice. To examine whether MAPA participates in biological reactions, hepatic and renal injury were induced by administration of CCl4 and HgCl2, respectively. MAPA-like activity was specifically increased in the injured tissues: the activity was elevated by about 100-fold in 48 h in the liver and increased by about 5-fold in 12 h in the kidney. Their enzymatic properties were the same as those of MAPA in 8C feline kidney fibroblast cells. Phospholipids are required for activation of prothrombin by MAPA obtained from both 8C cells and tissues. These results suggest that MAPA activates prothrombin on the cell surface in injured tissue and participates in inflammation and regeneration associated with tissue injury.
Shikamoto
Y
Y
Department of Biochemistry, Meiji College of Pharmacy, Tokyo, Japan.
Shibusawa
S
S
Okuyama
I
I
Morita
T
T
D000818:Animals; D001777:Blood Coagulation; D002251:Carbon Tetrachloride / Q000008:administration & dosage; D002460:Cell Line; D005260:Female; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007668:Kidney / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008627:Mercuric Chloride / Q000008:administration & dosage; D051379:Mice; D010743:Phospholipids / Q000502:physiology; D011516:Prothrombin / Q000737:chemistry* / Q000378:metabolism
D008565:Membrane Proteins; D010743:Phospholipids; D008627:Mercuric Chloride; D011516:Prothrombin; D002251:Carbon Tetrachloride