The Role of Oxidant for Matrix Metalloproteinase Activation in BPH through Computational Study

L Suhargo, SB Sumitro and Wido

Abstract

Benign Prostatic Hyperplasia (BPH) occurs due to interference of cell proliferation regulation. Two factor effects cell proliferation regulation are mitogen and antimitogen. The mitogen is growth factor and the one antimitogen is CD-26 or Dipeptidyl Peptidase-4 (DPP-4). DPP-4 could inhibit cell proliferation by blocking basic-Fibroblast Growth Factor (b-FGF). The expression of Dipeptidyl Peptidase-4 decreases due to damage or enzyme shedding from cell membrane. One of the factor that contribute to the Dipeptidyl Peptidase-4 shedding is Matrix Metalloproteinase (MMP) especially MMP-1, MMP-2 and MMP-9. The increasing of cell proliferation in BPH was also caused by collagen degradation. MMP could degrade collagen. So the activation of MMP was important in BPH. By computational study it was examined the interaction of ROS (Hydrogen Peroxide, Hydroxyl radical, Nitric Oxide and Superoxide) with MMP (MMP-1, MMP-2 and MMP-9). It was used Pathdock and Firedock program. Protein Structure of MMP could be obtained from UNIPROT and the structure of oxidant could be obtained from NCBI Pubchem Compound. The result showed that ROS could release propeptide domain of MMP-1,MMP-2 and MMP-9, then activate MMP.

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