Involvement of Fibronectin Type II Repeats in the Efficient Inhibition of Gelatinases A and B by Long-chain Unsaturated Fatty Acids

Alix Berton, Véronique Rigot, Eric Huet, Martine Decarme, Yves Eeckhout, L. Patthy, Gaston Godeau, William Hornebeck, Georges Bellon, Hervé Emonard

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Abstract

The matrix metalloproteinases gelatinase A (MMP-2) and gelatinase B (MMP-9) are implicated in the physiological and pathological breakdown of several extracellular matrix proteins. In the present study, we show that long-chain fatty acids (e.g. oleic acid, elaidic acid, and cis- and trans-parinaric acids) inhibit gelatinase A as well as gelatinase B with Ki values in the micromolar range but had only weak inhibitory effect on collagenase-1 (MMP-1), as assessed using synthetic or natural substrates. The inhibition of gelatinases depended on fatty acid chain length (with C18 > C16, C14, and C10), and the presence of unsaturations increased their inhibitory capacity on both types of gelatinase. Ex vivo experiments on human skin tissue sections have shown that micromolar concentrations of a long-chain unsaturated fatty acid (elaidic acid) protect collagen and elastin fibers against degradation by gelatinases A and B, respectively. In order to understand why gelatinases are more susceptible than collagenase-1 to inhibition by long-chain fatty acids, the possible role of the fibronectin-like domain (a domain unique to gelatinases) in binding inhibitory fatty acids was investigated. Affinity and kinetic studies with a recombinant fibronectin-like domain of gelatinase A and with a recombinant mutant of gelatinase A from which this domain had been deleted pointed to an interaction of long-chain fatty acids with the fibronectin-like domain of the protease. Surface plasmon resonance studies on the interaction of long-chain fatty acids with the three individual type II modules of the fibronectin-like domain of gelatinase A revealed that the first type II module is primarily responsible for binding these compounds.

Original languageEnglish
Pages (from-to)20458-20465
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number23
DOIs
Publication statusPublished - Jun 8 2001

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Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Unsaturated Fatty Acids
Fibronectins
Gelatinases
Fatty Acids
Matrix Metalloproteinases
Surface Plasmon Resonance
Elastin
Extracellular Matrix Proteins
Surface plasmon resonance
Oleic Acid
Chain length
Skin
Peptide Hydrolases
Collagen
Tissue
Degradation
Kinetics
Fibers

ASJC Scopus subject areas

  • Biochemistry

Cite this

Involvement of Fibronectin Type II Repeats in the Efficient Inhibition of Gelatinases A and B by Long-chain Unsaturated Fatty Acids. / Berton, Alix; Rigot, Véronique; Huet, Eric; Decarme, Martine; Eeckhout, Yves; Patthy, L.; Godeau, Gaston; Hornebeck, William; Bellon, Georges; Emonard, Hervé.

In: Journal of Biological Chemistry, Vol. 276, No. 23, 08.06.2001, p. 20458-20465.

Research output: Contribution to journalArticle

Berton, A, Rigot, V, Huet, E, Decarme, M, Eeckhout, Y, Patthy, L, Godeau, G, Hornebeck, W, Bellon, G & Emonard, H 2001, 'Involvement of Fibronectin Type II Repeats in the Efficient Inhibition of Gelatinases A and B by Long-chain Unsaturated Fatty Acids', Journal of Biological Chemistry, vol. 276, no. 23, pp. 20458-20465. https://doi.org/10.1074/jbc.M011664200
Berton, Alix ; Rigot, Véronique ; Huet, Eric ; Decarme, Martine ; Eeckhout, Yves ; Patthy, L. ; Godeau, Gaston ; Hornebeck, William ; Bellon, Georges ; Emonard, Hervé. / Involvement of Fibronectin Type II Repeats in the Efficient Inhibition of Gelatinases A and B by Long-chain Unsaturated Fatty Acids. In: Journal of Biological Chemistry. 2001 ; Vol. 276, No. 23. pp. 20458-20465.
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AU - Patthy, L.

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