Bronchopulmonary dysplasia and oxidative stress: are we closer to an understanding of the pathogenesis of BPD?

Saugstad, Ola Didrik

doi:10.1111/j.1651-2227.1997.tb14897.x

Cited by 119 publications

(60 citation statements)

References 63 publications

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“…The animal model we used mimics some pathologic features of BPD, such as increased inflammation, fibrosis, and septal thickness; decreased RAC and alveolar formation. These results are consistent with previous reports that hyperoxia can induce lung injury and disrupt alveolar septation at the critical stages of lung development (30,31).…”

Section: Discussionsupporting

confidence: 83%

Heat Shock Protein 27 Protects Lung Epithelial Cells From Hyperoxia-Induced Apoptotic Cell Death

et al. 2009

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ABSTRACT:Oxygen toxicity or hyperoxia is one of the major contributing factors in the development of bronchopulmonary dysplasia. Heat shock protein 27 (Hsp27) is an important chaperone protein in the postnatal lung development. However, the role of Hsp27 in lung epithelial cells during hyperoxia is unclear. Our studies by cDNA array and immunohistochemistry revealed that hyperoxia decreased Hsp27 expression in newborn rat lungs. Western blot showed that hyperoxic treatment significantly decreased Hsp27 protein expression in cultured human lung epithelial cells (A549). The expression of Hsp27 was decreased approximately twofold after 24-h and threefold after 48-and 72-h hyperoxic exposure compared with that of the A549 cells exposed to normoxia (p Ͻ 0.05, n ϭ 3). Knockdown of Hsp27 expression by siRNA resulted in more apoptotic cell death in A549 cells. Overexpression of Hsp27 reduced hyperoxia-induced apoptotic cell death to 9.2% in Hsp27 overexpressing A549 cells from 12.6% in control A549 cells after 72-h hyperoxic exposure (p Ͻ 0.01, n ϭ 8 -9). Overexpression of Hsp27 also diminished hyperoxia-induced caspase-9 activation in A549 cells. Our results demonstrated that hyperoxia decreased Hsp27 expression in newborn rat lung and cultured human lung epithelial cells. Overexpression of Hsp27 could reduce hyperoxia-induced apoptosis in cultured human lung epithelial cells. (Pediatr Res 65: 328-333, 2009) B ronchopulmonary dysplasia (BPD) is a chronic lung disease that typically occurs in premature infants with very low birth weight after supplemental oxygen therapy and mechanical ventilation. BPD, ranked with cystic fibrosis and asthma, is among the most common chronic lung diseases of infants in the United States (1). It is generally believed that oxygen toxicity or hyperoxia is one of the major contributing factors in the development of BPD. Hyperoxic lung injury is characterized by cell injury and cell death in pulmonary alveolar epithelial cells and capillary endothelial cells, which lead to impaired gas exchange (2,3). Premature infants are especially susceptible to oxidant-induced injury because their lungs are immature and the endogenous antioxidant enzyme activity is relatively deficient (4,5).Reactive oxygen species (ROS) generated during supplemental oxygen therapy are extremely cytotoxic. ROS causes protein dysfunction, cell membrane destruction, DNA damage, and cell death (6,7). Decreased antioxidant capacity of lung tissue during hyperoxia may contribute to the lung injury (4,5). The elimination of excess ROS generation, either by blocking ROS formation or increasing antioxidant production, should result in reduced oxidative stress with ultimate protection of the cells from hyperoxia-induced cell death (8,9). Hyperoxia induces both apoptotic and nonapoptotic cell death in lung epithelial cells. Apoptosis in lung epithelial cells is a tightly regulated process. Hyperoxia may activate both intrinsic and extrinsic apoptosis pathways in lung epithelial cells (10 -12). Heat shock protein 27 (Hsp27, known as...

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Section: Discussionsupporting

confidence: 83%

Heat Shock Protein 27 Protects Lung Epithelial Cells From Hyperoxia-Induced Apoptotic Cell Death

et al. 2009

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“…Artificial ventilation is causing damage with high peak inspiratory pressures and high percentage of inhaled oxygen, causing the formation of oxygen radicals. Beside GA, gender and PDA, resuscitation measures and mechanical ventilation high concentrations in tracheal aspirate fluid of infants developing BPD (38). Analysing prenatal and postnatal risk factors for BPD in our cohort of infants with GA < 30 wks, prenatal inflammation was not identified as a risk factor for BPD.…”

Section: Discussionmentioning

confidence: 92%

Prenatal and postnatal risk factors for developing bronchopulmonary dysplasia

Gantar

Babnik

Cerar

et al. 2011

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“…[20][21][22] El efecto de la hiperoxia a través de radicales libres en los prematuros se ve favorecido por una disminución de mecanismos antioxidantes en este grupo de niños. 3,20,21 El estudio aleatorizado SUPPORT comparó dos rangos de objetivos de saturación de oxígeno en prematuros menores de 28 semanas durante toda su internación. 23 Estos autores reportaron que, si bien el rango bajo (85-89%) disminuyó el riesgo de retinopatía del prematuro y DBP, se asoció a mayor mortalidad.…”

Section: Discussionunclassified