Roles of thiol proteases and kininogens in induction and regulation of inflammation
| Project/Area Number |
62570138
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Nagoya City University Medical School |
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Principal Investigator |
SASAKI Makoto Nagoya City University Medical School, 医学部, 教授 (10080003)
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| Co-Investigator(Kenkyū-buntansha) |
KUNIMATSU Mitoshi Nagoya City University Medical School, 医学部, 助手 (70145746)
OHKUBO Iwao Nagoya City University Medical School, 医学部, 助教授 (80152073)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1988: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | Inflammation / Calpain / Chemotactic factor / アセチル化ペプチド / ロイコエグレッシン / 免疫グロブリン |
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| Research Abstract |
First, interaction of calpains with kininogens were studied. It was found that calcium ion was required for the binding and that the inhibition of calpains by kininogens was accompanied by a simultaneous fragmentation of kininogen and the autodigestion of calpain itself. It was also revealed that when high molecular weight kininogen was digested by plasmin, ALPHA_1-thiol proteinase inhibitor was generated, releasing kinin and fragment 1・2.
Second, we found that chemotactic activity for polymorphonuclear leucocytes (PMN) was produced in the autodigest of calpain 1 purified from human erythrocytes. An active peptide was isolated from the autodigest and its chemical structure was determined. It was an acetylated nonapeptide with a sequence of acetyl Ser-Glu-Glu-Ile-Ile-Thr-Pro-Val-Tyr. In comparison with the entire sequence of human calpain I, this peptide was compatible with the N-terminal amino acid sequence of the large subunit of calpain I, whose primary structure was deduced from cDNA sequence, except that the peptide was demetionyl and acetylated at the N-terminus. The peptide was chemically synthesized and the chemotactic activity was reconfirmed by both in vitro experiment: assay in chemotactic microchembers and in vivo experiment: histological abservations after subcutaneous injection of the peptide. Several other peptides with amino acid sequences in n-termini of large and small subunits of calpains I and II were also synthesized and the chemotactic activity was examined. In addition to the above peptide, acetylated tri-, tetra-, and nona-peptides with the amino acid sequence in n-terminus of small subunit were shown to have the chemotactic activity.
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Report
(3 results)
Research Products
(15 results)
