Abstract
Soluble elastin-derived peptides from alkaline or elastase hydrolysis of insoluble elastin, as well as tropoelastin, increase matrix metalloproteinase-2 (MMP-2) production by human skin fibroblasts in culture as determined by gelatin zymography and ELISA. Such an effect is time and concentration dependent; it can be reproduced by synthetic elastin: VGVAPG, PGAIPG, and laminin: LGTIPG, hexapeptides and inhibited by lactose and is therefore elastin receptor-mediated. The steady state levels of MMP-2 mRNAs are invariant following elastin-fibroblasts interaction. Inhibition of phospholipase C (D-609), ADP-ribosylation factor (brefeldin), protein kinase C (RO-318220) and phospholipase D (1-propanol) totally abolished the elastin-mediated increase of MMP-2 production. It suggested that the post-transcriptional mechanism controlling the elastin-mediated overproduction of MMP-2 involved a cascade leading to phospholipase D activation.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
ADP-Ribosylation Factors / antagonists & inhibitors
-
Animals
-
Brefeldin A / pharmacology
-
Bridged-Ring Compounds / pharmacology
-
Cattle
-
Dactinomycin / pharmacology
-
Elastin / chemistry
-
Elastin / pharmacology*
-
Electrophoresis, Polyacrylamide Gel
-
Enzyme Activation / drug effects
-
Enzyme Induction / drug effects
-
Enzyme Inhibitors / pharmacology
-
Enzyme-Linked Immunosorbent Assay
-
Fibroblasts / drug effects*
-
Fibroblasts / enzymology
-
Humans
-
Indoles / pharmacology
-
Lactose / pharmacology
-
Laminin / pharmacology
-
Matrix Metalloproteinase 2 / biosynthesis*
-
Matrix Metalloproteinase 2 / genetics
-
Matrix Metalloproteinase 3 / biosynthesis
-
Matrix Metalloproteinase 3 / genetics
-
Norbornanes
-
Nucleic Acid Synthesis Inhibitors / pharmacology
-
Peptide Fragments / chemical synthesis
-
Peptide Fragments / pharmacology*
-
Phosphatidylinositol Diacylglycerol-Lyase
-
Phospholipase D / metabolism
-
Protein Kinase C / antagonists & inhibitors
-
Protein Processing, Post-Translational / drug effects
-
Signal Transduction
-
Skin / cytology
-
Thiocarbamates
-
Thiones / pharmacology
-
Tropoelastin / chemistry
-
Tropoelastin / pharmacology
-
Type C Phospholipases / antagonists & inhibitors
Substances
-
Bridged-Ring Compounds
-
Enzyme Inhibitors
-
Indoles
-
Laminin
-
Norbornanes
-
Nucleic Acid Synthesis Inhibitors
-
Peptide Fragments
-
Thiocarbamates
-
Thiones
-
Tropoelastin
-
Dactinomycin
-
Brefeldin A
-
tricyclodecane-9-yl-xanthogenate
-
Elastin
-
Protein Kinase C
-
Type C Phospholipases
-
Phospholipase D
-
Matrix Metalloproteinase 3
-
Matrix Metalloproteinase 2
-
ADP-Ribosylation Factors
-
Phosphatidylinositol Diacylglycerol-Lyase
-
Lactose
-
Ro 31-8220