Captopril inhibits apoptosis in human lung epithelial cells: a potential antifibrotic mechanism
| Autor: | Kevin Flynn, Olivia Ibarra-Sunga, Antonio Bifero, Gerasimos Filippatos, Claudia Gidea, Bruce D. Uhal, Michael Papp, Raed Bargout |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Pulmonary and Respiratory Medicine
medicine.medical_specialty Programmed cell death Captopril Lung Neoplasms Physiology Pulmonary Fibrosis Apoptosis DNA Fragmentation Adenocarcinoma Biology Models Biological Mice Physiology (medical) Internal medicine Pulmonary fibrosis Tumor Cells Cultured medicine Animals Humans fas Receptor Lung Caspase 3 Caspase 1 Antibodies Monoclonal Epithelial Cells Cell Biology medicine.disease Endocrinology medicine.anatomical_structure Cell culture Enzyme inhibitor Caspases ACE inhibitor Cancer research biology.protein medicine.drug |
| Zdroj: | American Journal of Physiology-Lung Cellular and Molecular Physiology. 275:L1013-L1017 |
| ISSN: | 1522-1504 1040-0605 |
| DOI: | 10.1152/ajplung.1998.275.5.l1013 |
| Popis: | The angiotensin-converting enzyme inhibitor captopril has been shown to inhibit fibrogenesis in the lung, but the mechanisms underlying this action are unclear. Apoptosis of lung epithelial cells is believed to be involved in the pathogenesis of pulmonary fibrosis. For these reasons, we studied the effect of captopril on Fas-induced apoptosis in a human lung epithelial cell line. Monoclonal antibodies that activate the Fas receptor induced epithelial cell apoptosis as detected by chromatin condensation, nuclear fragmentation, DNA fragmentation, and increased activities of caspase-1 and -3. Apoptosis was not induced by isotype-matched nonimmune mouse immunoglobulins or nonactivating anti-Fas monoclonal antibodies. When applied simultaneously with anti-Fas antibodies, 50 ng/ml of captopril completely abrogated apoptotic indexes based on morphology, DNA fragmentation, and inducible caspase-1 activity and significantly decreased the inducible activity of caspase-3. Inhibition of apoptosis by captopril was concentration dependent, with an IC50 of 70 pg/ml. These data suggest that the inhibitory actions of captopril on pulmonary fibrosis may be related to prevention of lung epithelial cell apoptosis. |
| Databáze: | OpenAIRE |
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