Maintenance of Feeding-Induced Translation Initiation Complex Assembly in the Lungs of Hyperoxia-Exposed Newborn Rats

Growth failure is common among preterm infants with bronchopulmonary dysplasia (BPD). Hyperoxia, an etiologic factor for BPD, reduces pulmonary protein synthesis in continually nursing rat pups. To determine if hyperoxia-induced alterations in nutrient-sensitive translational regulatory kinase, mTOR (mammalian target of rapamycin) contributes to diminished initiation events, we examined the meal-stimulated mTOR activity and eukaryotic initiation factor 4F (eIF4F) assembly in four-day-old Sprague Dawley rats pups exposed to 24 hours of room air (RA) or 95% O2 (Ox). At 16 hours, pups were fasted by maternal separation for 8 hours and then fed cow’s milk-based formula or water. Fasting suppressed the phosphorylation of the mTOR substrate S6K1 in both RA and Ox animals, but meal-feeding had little effect in either group. While fasting failed to alter eIF4F assembly, feeding increased eIF4F assembly in both groups. Ox attenuated polysome aggregation during initiation under both fasting and fed conditions. Ox increased eIF2α phosphorylation, an mTOR-independent repressor of initiation, 60 minutes after feeding. These findings illustrate that hyperoxia has little negative effect on mTOR-mediated regulation of translation initiation and highlight eIF2α as a potential factor responsible for the diminished protein synthetic capacity of the O2 -treated lung.