elastin and 3-hydroxypyridine

Topics: 2-Aminoadipic Acid; Animals; Basement Membrane; Cells, Cultured; Chemical Phenomena; Chemistry; Collagen; Connective Tissue Diseases; Cross-Linking Reagents; Elastin; Histidine; Humans; Metabolism, Inborn Errors; Models, Molecular; Protein-Lysine 6-Oxidase; Pyridines; Rats

Sprague-Dawley rats were exposed for 6 h daily to 0.8 ppm of ozone and 14.4 ppm of nitrogen dioxide. Approximately 7 to 10 wk after the initiation of exposure, animals began to demonstrate respiratory insufficiency and severe weight loss. About half of the rats died between Days 55 and 78 of exposure; no overt ill effects were observed in animals exposed to filtered air, to ozone alone, or to nitrogen dioxide. Biochemical findings in animals exposed to ozone and nitrogen dioxide included increased lung content of DNA, protein, collagen, and elastin, which was about 300% higher than the control values. The collagen-specific crosslink hydroxy-pyridinium, a biomarker for mature collagen in the lung, was decreased by about 40%. These results are consistent with extensive breakdown and remodeling of the lung parenchyma and its associated vasculature. Histopathologic evaluation showed severe fibrosis, alveolar collapse, honeycombing, macrophage and mast cell accumulation, vascular smooth muscle hypertrophy, and other indications of severe progressive interstitial pulmonary fibrosis and end-stage lung disease. This unique animal model of progressive pulmonary fibrosis resembles the final stages of human idiopathic pulmonary fibrosis and should facilitate studying underlying mechanisms and potential therapy of progressive pulmonary fibrosis.

Topics: Administration, Inhalation; Animals; Collagen; Desmosine; Disease Models, Animal; DNA; Elastin; Environmental Exposure; Hydroxyproline; Lung; Male; Nitrogen Dioxide; Ozone; Proteins; Pulmonary Fibrosis; Pyridines; Rats; Rats, Sprague-Dawley; Survival Rate

During pregnancy the collagen content of the human uterus increases sevenfold and the elastin content increases fourfold to fivefold. The stable pyridinoline cross-link is found in uterine collagen at a level of 0.11 mol per mole of collagen. The same ratio, or a higher one, is found at the end of pregnancy, indicating that pyridinoline synthesis keeps pace with the rapid synthesis of collagen. This cross-link would participate in the maintenance of high mechanical strength of the uterus needed during parturition. Uterine elastin contains 2.4 residues of desmosine plus isodesmosine in 1000 residues of amino acids. This value falls to 0.95 at term, indicating that synthesis of desmosines does not keep pace with the synthesis of elastin. Therefore, desmosine measurements do not provide an accurate index of elastin changes in pregnancy. Collagen and elastin contents in nongravid uteri increase with successive pregnancies; the cross-links remain constant during this change.

Topics: Amino Acids; Collagen; Connective Tissue; Desmosine; Elastin; Female; Humans; In Vitro Techniques; Isodesmosine; Postpartum Period; Pregnancy; Pyridines; Reproduction; Uterus