Hypoxia and nitric oxide exposure promote apoptotic signaling in contractile pulmonary arterial smooth muscle but not in pulmonary epithelium
| Autor: | Nora Nolette, Fabiana Postolow, Shyamala Dakshinamurti, Martha Hinton, Jena Fediuk |
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| Rok vydání: | 2011 |
| Předmět: |
Pulmonary and Respiratory Medicine
Pathology medicine.medical_specialty Lung Necrosis business.industry Cell cycle Hypoxia (medical) medicine.disease Pulmonary hypertension Nitric oxide Andrology chemistry.chemical_compound medicine.anatomical_structure chemistry Apoptosis Pediatrics Perinatology and Child Health medicine Myocyte medicine.symptom business |
| Zdroj: | Pediatric Pulmonology. 46:1194-1208 |
| ISSN: | 8755-6863 |
| Popis: | Rationale Neonatal pulmonary hypertension is characterized by hypoxia, abnormal vascular remodeling, and impaired alveolarization. Nitric oxide (NO) regulates cell replication and activation of apoptosis. Our objective was to examine cell phenotype-specific effects of hypoxia and NO exposure on cumulative apoptotic signal in neonatal pulmonary epithelial cells and arterial smooth muscle. Design/Methods Primary cultured newborn porcine pulmonary arterial myocytes and epithelial cells were grown in normoxic (21% O2) or hypoxic conditions (10% O2). Myocyte phenotype was predetermined by serum-supplementation or -deprivation. Cells were exposed to sodium nitroprusside (10−7–10−4 M) or diluent for 3 days. Cell survival was estimated by MTT assay; BAX, Bcl-2, and cleaved caspase-3 by Western blot; cell cycle entry by laser scanning cytometry. Results Hypoxic epithelial cells exhibited a small increase in anti-apoptotic Bcl2, and decrease in BAX. Cell survival and active caspase-3 were unchanged. Exposure to NO had no impact on epithelial apoptosis, but initiated necrosis. In contractile myocytes, pro-apoptotic BAX abundance and caspase-3 activation were increased by hypoxia, augmented by NO exposure promoting apoptosis. Hypoxia decreased BAX/Bcl-2 ratio and promoted survival of synthetic myocytes; NO increased apoptosis of normoxic synthetic myocytes, but decreased apoptosis of hypoxic synthetic myocytes. Conclusion The effect of NO on pulmonary apoptosis is phenotype-dependent. A cumulative apoptotic effect of hypoxia and NO in vitro exerted on contractile myocytes may lead to contraction of this subpopulation, while synthetic myocyte survival and proliferation is enhanced by hypoxia and NO. Epithelial survival is unaffected. We speculate that alveolar rarefaction reported after neonatal hypoxia may arise from growth arrest in the vascular rather than the epithelial compartment. Pediatr Pulmonol. 2011; 46: 1194–1208. © 2011 Wiley Periodicals, Inc. |
| Databáze: | OpenAIRE |
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