Oxodesmosine and isooxodesmosine, candidates of oxidative metabolic intermediates of pyridinium cross-links in elastin.
We isolated two new dihydrooxopyridine cross-links, oxodesmosine (OXD) and isooxodesmosine (IOXD) from the acid hydrolysates of the bovine aortic elastin. OXD and IOXD were identified to have N-substituted 1,2-dihydro-2-oxopyridine and N-substituted 1,4-dihydro-4-oxopyridine skeletons, respectively, with three alpha-amino acid groups and mass of 495 (C23H37N5O7). These structures and distribution indicated that OXD and IOXD are oxidative metabolites generated from desmosine (DES) and isodesmosine (IDE), respectively, by reactive oxygen species (ROS). Effects of ROS derived from divalent metal (Fe2+, Cu2+)/H2O2 on DES, IDE, OXD, and IOXD in elastin were investigated. Changes in the contents of these cross-links in elastin were observed by using reverse-phase HPLC with UV detection. The time- and pH-dependent formation of OXD and reduction of DES and IDE in elastin by Cu2+/H2O2 and Fe2+/H2O2 were observed. OXD was found to be formed from DES by Fe2+/H2O2. No formation of IOXD was observed under the conditions of oxidation examined. By using a model compound of IDE, however, we found that 4-pyridone could be formed by Fe2+/H2O2. Elastin incubated in Cu2+/H2O2 was also solubilized dependent on solution pH and the concentration of H2O2. These results suggest that oxidative degradation of elastin with cross-links results in its weakening, followed by its solubilization. Pyridinium cross-links, such as DES and IDE, may be oxidatively metabolized by ROS, further changing to dihydrooxopyridine cross-links such as OXD and IOXD, respectively.
Umeda
H
H
Department of Applied Bioorganic Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
Nakamura
F
F
Suyama
K
K
D000818:Animals; D001011:Aorta / Q000737:chemistry; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D003895:Desmosine / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology*; D004549:Elastin / Q000737:chemistry* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D010100:Oxygen / Q000378:metabolism*; D011725:Pyridines / Q000737:chemistry*; D013053:Spectrophotometry; D013997:Time Factors; D014466:Ultraviolet Rays
D003432:Cross-Linking Reagents; D011725:Pyridines; D003895:Desmosine; C428432:oxodesmosine; C428433:isooxodesmosine; D004549:Elastin; D006861:Hydrogen Peroxide; C023666:pyridine; D010100:Oxygen