Browsing by Author "Ferrer-Marquez, Fernando"

Now showing 1 - 1 of 1
  • No Thumbnail Available
    Item
    Fetal lung hypoxia and energetic cell failure in the nitrofen-induced congenital diaphragmatic hernia rat model
    (2023) Romero-Lopez, Mar; Oria, Marc; Ferrer-Marquez, Fernando; Varela, Maria Florencia; Lampe, Kristin; Watanabe-Chailland, Miki; Martinez, Leopoldo; Peiro, Jose L. L.
    PurposeCongenital diaphragmatic hernia (CDH) pathogenesis is poorly understood. We hypothesize that fetal CDH lungs are chronically hypoxic because of lung hypoplasia and tissue compression, affecting the cell bioenergetics as a possible explanation for abnormal lung development.MethodsTo investigate this theory, we conducted a study using the rat nitrofen model of CDH. We evaluated the bioenergetics status using H1 Nuclear magnetic resonance and studied the expression of enzymes involved in energy production, the hypoxia-inducible factor 1 alpha, and the glucose transporter 1.ResultsThe nitrofen-exposed lungs have increased levels of hypoxia-inducible factor 1 alpha and the main fetal glucose transporter, more evident in the CDH lungs. We also found imbalanced AMP:ATP and ADP:ATP ratios, and a depleted energy cellular charge. Subsequent transcription levels and protein expression of the enzymes involved in bioenergetics confirm the attempt to prevent the energy collapse with the increase in lactate dehydrogenase C, pyruvate dehydrogenase kinase 1 and 2, adenosine monophosphate deaminase, AMP-activated protein kinase, calcium/calmodulin-dependent protein kinase 2, and liver kinase B1, while decreasing ATP synthase.ConclusionOur study suggests that changes in energy production could play a role in CDH pathogenesis. If confirmed in other animal models and humans, this could lead to the development of novel therapies targeting the mitochondria to improve outcomes.