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 enzymatic breakdown of human lung elastin by leukocyte elastase precedes the development of pulmonary emphysema, and releases elastin-derived peptides (EDPs) into the circulation. While raised levels of EDPs measured by enzyme-linked immunosorbent assay (ELISA) have been proposed as a possible marker for early detection of emphysema, average normal values of EDPs measured by different investigators have differed by up to a factor of 1000. Standardisation of the methodology for elastin purification and EDP production in vitro is required to ensure the accuracy of EDP measurements in vivo, because antiserum used in the ELISA is raised against the EDPs produced in vitro. In the present study elastin was purified from human lung by sequential biochemical extraction, and solubilised by leukocyte elastase. Molecular weight distribution of EDPs produced by partial and complete elastin digestion were compared by gel exclusion chromatography. A method for successful separation of EDPs by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) is reported. The implications of these results for further immunological characterisation of these peptides are discussed with a view to standardisation of the techniques employed for the measurement of EDPs in vivo.
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PMID:Characterisation of human lung elastin-derived peptides. 848 61

The scalene has been reported to be an accessory inspiratory muscle in the hamster. We hypothesize that with the chronic loads and/or dynamic hyperinflation associated with emphysema (Emp), the scalene will be actively recruited, resulting in functional, cellular, and biochemical adaptations. Emp was induced in adult hamsters. Inspiratory electromyogram (EMG) activity was recorded from the medial scalene and costal diaphragm. Isometric contractile and fatigue properties were evaluated in vitro. Muscle fibers were classified histochemically and immunohistochemically. Individual fiber cross-sectional areas (CSA) and succinate dehydrogenase (SDH) activities were determined quantitatively. Myosin heavy chain (MHC) isoforms were identified by SDS-PAGE, and their proportions were determined by scanning densitometry. All Emp animals exhibited spontaneous scalene inspiratory EMG activity during quiet breathing, whereas the scalene muscles of controls (Ctl) were silent. There were no differences in contractile and fatigue properties of the scalene between Ctl and Emp. In Emp, the relative amount of MHC(2A) was 15% higher whereas that of MHC(2X) was 14% lower compared with Ctl. Similarly, the proportion of type IIa fibers increased significantly in Emp animals with a concomitant decrease in IIx fibers. CSA of type IIx fibers were significantly smaller in Emp compared with Ctl. SDH activities of all fiber types were significantly increased by 53 to 63% in Emp. We conclude that with Emp the actively recruited scalene exhibits primary-like inspiratory activity in the hamster. Adaptations of the scalene with Emp likely relate both to increased loads and to factors intrinsic to muscle architecture and chest mechanics.
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PMID:Functional, cellular, and biochemical adaptations to elastase-induced emphysema in hamster medial scalene. 1074 27

Human alpha-1 antitrypsin (AAT) is an abundant serum protein present at a concentration of 1.0-1.5 g L(-1). AAT deficiency is a genetic disease that manifests with emphysema and liver cirrhosis due to the accumulation of a misfolded AAT mutant in hepatocytes. Lung AAT amount is inversely correlated with chronic obstructive pulmonary disease (COPD), a serious and often deadly condition, with increasing frequency in the aging population. Exposure to cigarette smoke and products of fossil fuel combustion aggravates AAT deficiency and COPD according to mechanisms that are not fully understood. Taking into account that these fumes contain particles that can release nickel to human airways and skin, we decided to investigate interactions of AAT with Ni(ii) ions within the paradigm of Ni(ii)-dependent peptide bond hydrolysis. We studied AAT protein derived from human blood using HPLC, SDS-PAGE, and mass spectrometry. These studies were aided by spectroscopic experiments on model peptides. As a result, we identified three hydrolysis sites in AAT. Two of them are present in the N-terminal part of the molecule next to each other (before Thr-13 and Ser-14 residues) and effectively form one N-terminal cleavage site. The single C-terminal cleavage site is located before Ser-285. The N-terminal hydrolysis was more efficient than the C-terminal one, but both abolished the ability of AAT to inhibit trypsin in an additive manner. Nickel ions bound to hydrolysis products demonstrated an ability to generate ROS. These results implicate Ni(ii) exposure as a contributing factor in AAT-related pathologies.
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PMID:Ni(ii) ions cleave and inactivate human alpha-1 antitrypsin hydrolytically, implicating nickel exposure as a contributing factor in pathologies related to antitrypsin deficiency. 2557 32