Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the changes in collagen metabolism that occur in the pathogenesis of pulmonary fibrosis, female rats were exposed to 0, 0.57, and 1.1 ppm ozone for 19 hr/day for 11 days and sacrificed 12 or 60 days after initiation of exposure. The lungs of rats sacrificed at 12 days after initiation of exposure to 1.1 ppm had interstitial pneumonia characterized by a mixed inflammatory cell infiltrate, type II cell hyperplasia, and fibroplasia, a proliferation of the collagen-producing cells; increased cathepsin D and macrophage elastase activity, indicating macrophage-induced proteinolysis; a reduced percentage of the increased collagen production that was ultrafilterable, indicating a decreased rate of intracellular degradation of newly produced collagen prior to its secretion; and increased lavage fluid hydroxyproline, indicating turnover of extracellular collagenous matrix. Reduced intracellular collagen degradation correlated directly with both increased net collagen production and fibroplasia in rats exposed to 1.1 ppm ozone for 11 days. These changes preceded an increased total lung collagen and the development of modest fibroplasia and fibrosis in the alveolar duct regions by 60 days after the 1.1 ppm ozone exposure was initiated.
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PMID:Changes in collagen metabolism and proteinolysis after repeated inhalation exposure to ozone. 303 Jul 98

Amiodarone (AD) is a highly efficient antiarrhythmic drug with potentially serious side effects. Severe pulmonary toxicity is reported in patients receiving AD even at low doses and may cause interstitial pneumonia as well as lung fibrosis. Apoptosis of alveolar epithelial type II cells (AECII) has been suggested to play an important role in this disease. In the current study, we aimed to establish a murine model of AD-induced lung fibrosis and analyze surfactant homeostasis, lysosomal, and endoplasmic reticulum (ER) stress in this model. AD/vehicle was instilled intratracheally into C57BL/6 mice, which were sacrificed on days 7, 14, 21, and 28. Extent of lung fibrosis development was assessed by trichrome staining and hydroxyproline measurement. Cytotoxicity was assessed by lactate dehydrogenase assay. Phospholipids (PLs) were analyzed by mass spectrometry. Surfactant proteins (SP) and markers for apoptosis, lysosomal, and ER stress were studied by Western blotting and immunohistochemistry. AECII morphology was evaluated by electron microscopy. Extensive lung fibrosis and AECII hyperplasia were observed in AD-treated mice already at day 7. Surfactant PL and SP accumulated in AECII over time. In parallel, induction of apoptosis, lysosomal, and ER stress was encountered in AECII of mice lungs and in MLE12 cells treated with AD. In vitro, siRNA-mediated knockdown of cathepsin D did not alter the AD-induced apoptotic response. Our data suggest that mice exposed to intratracheal AD develop severe pulmonary fibrosis, exhibit extensive surfactant alterations and cellular stress, but AD-induced AECII apoptosis is not mediated primarily via cathepsin D.
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PMID:Altered surfactant homeostasis and alveolar epithelial cell stress in amiodarone-induced lung fibrosis. 2516 75