Figure 11
Apoptosis signaling and pathways. (A) Schematic model for apoptosis pathways in the perinatal alveolar epithelium. Exposure to ascending ΔpO2 regimen and reactive oxygen species (ROS), a process referred to as chemioxyexcitation, triggers a signaling mechanism that could lead to either apoptosis or activation of NF-κB. NF-κB conveys a protective effect by amplifying Bcl-2 through the antagonism (anti-apoptotic) survival loop. Whereas thiols such as N-acetyl-L-cysteine (NAC) and γ-glutamylcysteinyl-ethyl ester (γ-GCE) promote the survival loop, sulfasalazine (SSA), a selective inhibitor of NF-κB, confers negative regulation favoring apoptosis. Glutathione depletion by L-buthionine-(S,R)-sulfoximine (BSO) upregulates the expression of Bax and p53 through activation of the agonism (pro-apoptotic) death loop, an effect that is mimicked by pyrrolidine dithiocarbamate (PDTC). The likely 'executioners' implicated in apoptosis are the caspases, the final effectors in the death machinery. (B) Schematic model for apoptosis pathways in the perinatal developing lung. The transition from placental to lung-based respiration during the birth transition period constitutes a potential signaling mechanism in the lung. This represents a relative hyperoxic shift, which allows the differential expression of signaling cofactors involved in apoptosis. The downstream pathway mediates suppression of Bcl-2 with pulmonary oxygenation, a phenomenon accompanied by down-regulating Bax. The major participant in regulating cell death ex utero is p53, which switches off the induction of Bcl-2 and rather predominates Bax in controlling apoptosis within the perinatal lung. This reinforces the presumption that signaling pathways mediating apoptosis in response to oxygenation in the developing lung are p53-dependent. The (+) sign indicated positive modulation (up-regulation) and (-) sign indicates negative modulation (down-regulation).