Analysis of fibrinolytic activation mechanism by staphylokinase in gene deficient mice
Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants|
|Research Institution||Kinki University|
OKADA Kiyotaka Kinki University School of Medicine, 2nd Physiology, Assistant, 医学部, 助手 (20185432)
FUKAO Hideharu Kinki University School of Medicine, 2nd Physiology, Assistant, 医学部, 助手 (70218874)
UESHIMA Shigeru Kinki University School of Medicine, 2nd Physiology, Assistant Professor, 医学部, 助教授 (30193791)
MATSUO Osamu Kinki University School of Medicine, 2nd Physiology, Professor, 医学部, 教授 (40030879)
|Project Period (FY)
1997 – 1998
Completed(Fiscal Year 1998)
|Budget Amount *help
¥3,100,000 (Direct Cost : ¥3,100,000)
Fiscal Year 1998 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1997 : ¥2,000,000 (Direct Cost : ¥2,000,000)
|Keywords||staphylokinase / plasminogen / plasminogen activator / alpha2-antiplasmin / gene deficient mice / α_2ーアンチプラスミン|
Staphylokinase (SAK) expresses plasminogen activator (PA) activity by forming a complex with plasminogen (Pig) or plasmin. Although this PA activity is inhibited by alpha2-antiplasmin (alpha2-AP), its activity is protected against the inhibition by alpha2-AP in the presnce of fibrin. The interaction between SAK and Pig were investigated using mutant SAKs, synthetic SAK peptides, purified pigs of several animals and gene deficient mice plasma.
1). The interaction between mutant SAKs and pig.
The deleted mutants of NH2-terminal amino acid region of SAK contracted by lacking the first 14, 18 and 25 amino acid region ( 14 SAK, 18 SAK and 25 SAK). The11-14 amino acid region of SAK was necessary to express PA activity after binding with Glu-plg.
2). The interaction between synthetic SAK peptides and pig.
The SAK peptides synthesized peptides consisted 10-30 amino acid in SAK amino acid sequence. The synthetic SAK peptides did not show PA activity. However, the synthetic nonadecapeptide (Glu22-Leu4O) of SAK bound to Glupig pig and enhanced pig activation by native SAK.
3). The alpha2-AP and Pig gene deficient mice.
The alpha2-AP gene deficient mice (alpha2-AP-/-) obtained by cloning and targeting of murine alpha2-AP gene. The pig gene deficient mice (Pig-/-)established breeding method and assay methods of pig gene in mice.
4). The interaction between SAK and purified pigs in buffer and in alpha2-AP or Pig deficient mice plasma.
The pigs purified from plasma of human, mice, rabbit or bovine. The interaction between SAK and purified pigs investigated in buffer and in alpha2-AP-/- or Pig-/- mice plasma. These findings indicate that (1) murine or bovine plg dose not react with SAK, (2) SAK-human piasmin complex activates murine or bovine plg, and (3) this murine plg activation is inhibited by murine alpha2-AP.
Research Output (8results)