-Hematin Interaction with the Hemopexin Domain of Gelatinase B/MMP-9 Provokes Autocatalytic Processing of the Propept
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- 作者：Nathalie Geurts ; Erik Martens ; Ilse Van Aelst ; Paul Proost ; Ghislain Opdenakker ; Philippe E. Van den Steen
- 刊名：Biochemistry
- 出版年：2008
- 出版时间：February 26, 2008
- 年：2008
- 卷：47
- 期：8
- 页码：2689 - 2699
- 全文大小：894K
- 年卷期：v.47,no.8(February 26, 2008)
- ISSN：1520-4995
文摘
Gelatinase B or matrix metalloproteinase-9 is involved in inflammation and in autoimmuneand vascular diseases. In contrast to the constitutive and homeostatic matrix metalloproteinase-2, matrixmetalloproteinase-9 is an inducible enzyme. Furthermore, it needs tight regulation, and a major controlmechanism of its enzymatic activity is the activation of the latent enzyme by proteolysis of the 87 residuepropeptide. Activated matrix metalloproteinase-9 is detected in many vascular or hematological diseasestates, including in an experimental model for cerebral malaria with Plasmodium berghei ANKA. However,insight into its activation mechanism is incomplete. In view of the association with hemorrhagic andhemolytic diseases, it was studied whether and how hemoglobin and its derivatives might activate pro-matrix metalloproteinase-9. Incubation of matrix metalloproteinase-9 with hemin or 
hars/beta2.gif" BORDER=0 ALIGN="middle">-hematin, the coreconstituent of hemozoin or malaria pigment, leads to differential autocatalysis of the propeptide, mediatedby allosteric interaction with the hemopexin domain. The cleavage catalyzed by hars/beta2.gif" BORDER=0 ALIGN="middle">-hematin coincideswith the first cleavage by stromelysin-1/matrix metalloproteinase-3, and preincubation of matrixmetalloproteinase-9 with hars/beta2.gif" BORDER=0 ALIGN="middle">-hematin enhances the activation rate by matrix metalloproteinase-3 at least6-fold. These findings suggest that reduction of hemorrhage and hemolysis might prevent matrixmetalloproteinase-9-mediated inflammatory and vascular damages.
hars/beta2.gif" BORDER=0 ALIGN="middle">-hematin, the coreconstituent of hemozoin or malaria pigment, leads to differential autocatalysis of the propeptide, mediatedby allosteric interaction with the hemopexin domain. The cleavage catalyzed by hars/beta2.gif" BORDER=0 ALIGN="middle">-hematin coincideswith the first cleavage by stromelysin-1/matrix metalloproteinase-3, and preincubation of matrixmetalloproteinase-9 with hars/beta2.gif" BORDER=0 ALIGN="middle">-hematin enhances the activation rate by matrix metalloproteinase-3 at least6-fold. These findings suggest that reduction of hemorrhage and hemolysis might prevent matrixmetalloproteinase-9-mediated inflammatory and vascular damages.