Treatment with Geranylgeranylacetone Induces Heat Shock Protein 70 and Attenuates Neonatal Hyperoxic Lung Injury in a Model of Bronchopulmonary Dysplasia
| Autor: | Hironobu Naiki, Shuko Tokuriki, Aiko Igarashi, Yusei Ohshima, Takashi Okuno, Genrei Ohta |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Alveolarization Gestational Age Lung injury Hyperoxia Article Andrology 03 medical and health sciences 0302 clinical medicine Heat shock protein Parenchyma medicine Animals Humans HSP70 Heat-Shock Proteins Lung TUNEL assay business.industry Oxygen Inhalation Therapy Lung Injury respiratory system medicine.disease Bronchopulmonary dysplasia Hsp70 Failure to Thrive Up-Regulation Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Animals Newborn Cytoprotection 030220 oncology & carcinogenesis Anesthesia Geranylgeranylacetone medicine.symptom Diterpenes business Infant Premature |
| Zdroj: | Lung |
| ISSN: | 1432-1750 |
| Popis: | Purpose Bronchopulmonary dysplasia (BPD) is a respiratory complication characterized by abnormal alveolar development in premature infants. Geranylgeranylacetone (GGA) can induce heat shock protein (HSP) 70, which has cytoprotective effects against various stressors. Here, we investigated whether GGA protected neonatal lungs from hyperoxic stress in a murine BPD model, and measured the serum HSP70 levels in preterm humans treated with oxygen. Methods Newborn mice were exposed to >90% oxygen and administered GGA or vehicle alone orally on days 1, 2, and 3 of life. At 2 days of age, HSP70 expression in the lung was determined by western blotting. At 8 days of age, the lungs were processed for histological analysis. Radial alveolar count (RAC) and mean linear intercept (MLI) were measured as parameters of alveolarization. Apoptosis was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method and cleaved caspase-3 immunohistochemistry. Serum HSP70 levels in preterm humans treated with oxygen were measured by enzyme-linked immunosorbent assay. Results GGA administration enhanced the HSP70 expression to two-fold compared with normoxia-exposed and vehicle-treated mice. Hyperoxia reduced HSP70 expression, whereas GGA abrogated the effects. Hyperoxia-exposed mice exhibited more apoptotic cells in lung parenchyma and a more simplified alveolar structure with less RAC and larger MLI than normoxia-exposed mice. GGA suppressed the increase in apoptotic cells and the structural changes of the lungs induced by hyperoxia. Serum HSP70 levels of preterm human infants gradually decreased with age. Conclusions GGA may attenuate hyperoxic injury in neonatal lungs and thereby may prevent the development of BPD. |
| Databáze: | OpenAIRE |
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