Measurement of cross-linked elastin synthesis in bleomycin-induced pulmonary fibrosis using a highly sensitive assay for desmosine and isodesmosine.
Cross-linked elastin synthesis was measured in the intratracheal bleomycin model of interstitial pulmonary fibrosis by incorporation of 14C-lysine into the elastin-specific crosslinks, desmosine and isodesmosine. Detection of the labeled crosslinks was facilitated by development of a highly sensitive assay utilizing thin-layer electrophoresis. The results indicate that crosslinked elastin synthesis is significantly elevated from controls (p less than 0.05) at 1 to 3 weeks after exposure to bleomycin and returns to normal by 5 weeks. The increases in labeled elastin synthesis are not directly related to changes in either total lung protein synthesis or the pool size of the 14C-lysine. In comparison with collagen and glycosaminoglycan synthesis in this model of lung injury, maximal increases in cross-linked elastin formation occur later, but overlap with the elevated synthesis of these other connective tissue components. The marked increase from normal in cross-linked elastin synthesis in this model suggests that this tissue component is an important part of the fibrotic response of the pulmonary parenchyma and may play a role in the observed alterations in lung structure and function.
D000596:Amino Acids; D000818:Animals; D001761:Bleomycin; D002250:Carbon Radioisotopes; D006224:Cricetinae; D003895:Desmosine / Q000032:analysis; D004549:Elastin / Q000096:biosynthesis*; D005260:Female; D007524:Isodesmosine / Q000032:analysis; D008239:Lysine / Q000378:metabolism; D008647:Mesocricetus; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism*
D000596:Amino Acids; D002250:Carbon Radioisotopes; D003895:Desmosine; D001761:Bleomycin; D004549:Elastin; D007524:Isodesmosine; D008239:Lysine