Injury-induced enzymatic methylation of aging collagen in the extracellular matrix of blood vessels.
As a result of blood vessel injury, protein D-aspartyl/L-isoaspartyl carboxyl methyltransferase (PIMT), a normally intracellular enzyme, becomes trapped within the meshwork of the vascular extracellular matrix where it can methylate substrate proteins. In this investigation we examined the distribution of such altered aspartyl-containing substrate proteins in the vascular wall. Nearly 90% of all the altered aspartyl residues were inaccessible to intracellular PIMT. Proteins of the extracellular matrix were found to be the major repository of altered aspartyl-containing polypeptides in the blood vessel wall, accounting for approximately 70% of the total amount. Proteolytic cleavage of extracellular matrix proteins with cyanogen bromide (CNBr) revealed that collagens account for most of the altered aspartyl-containing proteins of the ECM. As a consequence of blood vessel injury, both type I and type III collagen along with other proteins were found to become methylated by injury-released PIMT. It is estimated that 1 cm of vein contains on the order of 5 x 10(14) altered aspartyl residues involving between 1% and 5% of the total extracellular protein.
Weber
D J
DJ
Department of Biochemistry and Biophysics, Oregon State University, Corvallis 97331, USA.
McFadden
P N
PN
D000818:Animals; D001808:Blood Vessels / Q000737:chemistry / Q000201:enzymology* / Q000293:injuries*; D016922:Cellular Senescence; D003094:Collagen / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D004730:Endothelium, Vascular / Q000737:chemistry / Q000166:cytology / Q000201:enzymology; D005109:Extracellular Matrix / Q000737:chemistry / Q000201:enzymology*; D005260:Female; D008745:Methylation; D010477:Perfusion; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase; D011496:Protein Methyltransferases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D003094:Collagen; D011496:Protein Methyltransferases; D026601:Protein D-Aspartate-L-Isoaspartate Methyltransferase