Etude du rôle de PARP-1 dans la mort cellulaire induite par l'oxygène

Les lésions aigues du poumon sont consécutives à différentes étiologies, dont l'exposition à des concentrations élevées en oxygène. Le stress oxydatif résultant de l'hyperoxie induit la mort des cellules endothéliales, formant la barrière alvéolo-capillaire, responsable des échanges gazeux pulmonaires. Dans ce travail nous avons étudié le rôle de la molécule Poly- (ADP-Ribose) Polymerase-1 (PARP-1) impliqué dans la réparation de l'ADN, ainsi que dans la mort cellulaire. Dans cette optique, nous avons étudié le rôle de PARP-1 dans la mort cellulaire induite par l'oxygène, ainsi que dans la répartition cellulaire "in vitro" et "in vivo". Nos résultats démontrent le rôle essentiel de PARP-1 dans le contrôle de la réparation cellulaire et le remodelage tissulaire, induit lors de lésions pulmonaires dues à l'oxygène. Cependant, le rôle de PARP-1 dans le mécanisme aigu de mort cellulaire semble complexe et dépendant du type cellulaire analysé

Gestation and lactation exposure to nicotine induces transient postnatal changes in lung alveolar development.

Harmful consequences of cigarette smoke (CS) exposure during lung development can already manifest in infancy. In particular, early life exposure to nicotine, the main component of CS, was shown to affect lung development in animal models. We aimed to characterize the effect of nicotine on alveoli formation. We analyzed the kinetics of normal alveolar development during the alveolarization phase and then looked at the effect of nicotine in a mouse model of gestational and early life exposure. Immunohistochemical staining revealed that the wave of cell proliferation (i.e. vascular endothelial cells, alveolar epithelial cells (AEC) type II and mesenchymal cell) occurs at pnd8 in control and nicotine-exposed lungs. However, FACS analysis of individual epithelial alveolar cells revealed nicotine-induced transient increase of AEC type I proliferation and decrease of vascular endothelial cell proliferation at pnd8. Furthermore, nicotine increased the percentage of endothelial cells at pnd2. Transcriptomic data also showed significant changes in nicotine samples compared to the controls on cell cycle associated genes at pnd2, but not anymore at pnd16. Accordingly, the expression of survivin, involved in cell cycle regulation, also follows a different kinetics in nicotine lung extracts. These changes resulted in an increased lung size detected by stereology at pnd16, but no longer in adult age, suggesting that nicotine can act on the pace of lung maturation. Taken together, our results indicate that early life nicotine exposure could be harmful to alveolar development independently from other toxicants contained in CS

NADPH Oxidase-1 Plays a Crucial Role in Hyperoxia-induced Acute Lung Injury in Mice

Rationale: Hyperoxia-induced acute lung injury has been used for many years as a model of oxidative stress mimicking clinical acute lung injury and the acute respiratory distress syndrome. Excess quantities of reactive oxygen species (ROS) are responsible for oxidative stress–induced lung injury. ROS are produced by mitochondrial chain transport, but also by NADPH oxidase (NOX) family members. Although NOX1 and NOX2 are expressed in the lungs, their precise function has not been determined until now