MMP-9- jarrutus poistamalla sen plasmiinilla aktivoituminen palautumattomasti alendronaatilla

FEBS Lett. 2012 Jul 30;586(16):2366-74. doi: 10.1016/j.febslet.2012.05.048. Epub 2012 Jun 4. Alendronate promotes plasmin-mediated MMP-9 inactivation by exposing cryptic plasmin degradation sites within the MMP-9 catalytic domain.

Farina AR¹, Cappabianca L, Di Ianni N, Ruggeri P, Ragone M, Merolle S, Gulino A, Mackay AR.

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Abstract

Irreversible MMP-9 inhibition is considered a significant therapeutic goal in inflammatory, vascular and tumour pathology. We report that divalent cation chelators Alendronate and EDTA not only directly inhibited MMP-9 but also promoted irreversible plasmin-mediated MMP-9 inactivation by exposing cryptic plasmin-degradation sites within the MMP-9 catalytic-domain and producing an inhibitory hemopexin-domain fragment. This effect was also observed using MDA-MB-231 breast cancer cells, which activated exogenous plasminogen to degrade endogenous proMMP-9 in the presence of Alendronate or EDTA. Degradation-mediated inactivation of proMMP-9 occurred in the absence of transient activation, attesting to the incapacity of plasmin to directly activate proMMP-9 and direct MMP-9 inhibition by Alendronate and EDTA. Our study provides a novel rational for therapeutic Alendronate use in MMP-9-dependent pathology characterised by plasminogen activation.

(Kommentti: Alendronaattia on esim Fosamax)