Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The protease-antiprotease imbalance concept has gained wide acceptance in reference to experimental animal models of human pulmonary emphysema. The destructive process may be induced by proteolytic enzymes such as porcine pancreas elastase (E) or papain (P), or by oxidants such as chloramine T (CT) which cause inactivation of alpha-1-antiprotease. The susceptibility to development of severe emphysema has been found to differ among animal species. We investigated the inhibition of elastase and papain by serum of seven species (rat, dog, human, rabbit, sheep, hamster, mini pig) and the effect of CT on serum inhibition. The relative inhibitor concentration of serum was expressed in terms of its inhibitor capacity for elastase and papain (EIC and PIC) defined as number of inhibited units (U) of enzyme catalysed hydrolysis of chromogenic peptide substrate (SAPNA and BAPNA) per unit of serum. The effect of CT on enzyme inhibition was quantified in terms of fractional loss of inhibition relative to control. The serum concentration of inhibitor was highest in the rat (EIC 8642 +/- 989 microU/microliter, PIC 214.2 +/- 110.3 microU/microliter; means +/- SD). Next in order of decreasing EICs were dog, human, rabbit, sheep, hamster, and mini pig exhibiting the lowest EIC (2523 +/- 184 microU/microliter) while sheep had lowest PIC (39.6 +/- 3.5 microU/microliter). The EIC/PIC ratio varied from 20 (mini pig) to about 100. The reduction of elastase inhibition after CT exposure of serum was high (80-100%) in rat, dog, human, and hamster, moderate (40%) in mini pig and rabbit, and low (10%) in sheep. Because papain was directly affected by CT the effect of CT on papain inhibition could not be analysed. The data suggest that the intrinsic antiprotease and antioxidant screen varies among experimental animals. For the purpose of animal models of emphysema, hamster appears to be most susceptible to the progressive destruction of lung parenchyma elicited by experimental burden of proteases or oxidants.
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PMID:Elastase and papain inhibition by serum of mammals. 274 Aug 28

When alpha-1-PI is oxidized, it loses its ability to inhibit porcine elastase, although it retains its TIC. Therefore the ratio of TIC to EIC increases in proportion to the degree of oxidation of the inhibitor. We have developed a rapid procedure for determining the percentage of oxidized alpha-1-PI in plasma or serum based on the ratio of TIC to EIC of alpha-1-PI in these tissues. The TIC/EIC ratio is not influenced by the other proteins in serum nor by the concentration of alpha-1-PI. When this technique was adapted to measure to proportion of oxidized alpha-1-PI in the serum of young adult, healthy smokers and nonsmokers, 23% oxidized inhibitor was found in the smokers' sera, whereas no oxidized alpha-1-PI was detectable in sera of nonsmokers. Thus smoking leads to oxidation damage to circulating alpha-1-PI. Reduction of the EIC of the alpha-1-PI in the serum of smokers was compensated by a 1.43-fold increase in their serum alpha-1-PI titers; however, these data do not exclude the possibility of local depletion of the absolute EIC in the extravascular space of the lungs. This assay for oxidized alpha-1-PI may be useful in studies of the relationship between oxidation of alpha-1-PI and the development of pulmonary emphysema.
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PMID:Determination of oxidized alpha-1-proteinase inhibitor in serum. 617 85