The juxtaposition of Taurine in Bronchopulmonary Dysplasia

Background: Metabolic dysregulation has been implicated in bronchopulmonary dysplasia development. Taurine is an essential amino acid for neonates and is critically involved in glucose and fatty acid metabolism. Neonatal tissue obtains taurine mainly through the taurine transporter. The biological role of taurine in neonatal lung development has never been explored. As glucose metabolism mechanistically modulates angiogenesis and angiogenesis is the central player for neonatal lung development, we hypothesize that taurine depletion contributes to bronchopulmonary dysplasia development. Results: Although most genes and proteins for oxidative phosphorylation were enriched in hyperoxia pup lungs, the complex-1 activity decreased. The decrease in taurine-dependent complex-1 core subunits, ND5 and ND6, in hyperoxia lungs reasonably explained the discrepancy. Metabolomics analysis demonstrated decreased lung taurine with increased blood taurine of hyperoxia pups, compatible with the decreased taurine transporter expression. Decreased glycosylation and increased degradation explained the decreased taurine transporter expression. The results of the complementary study using tunicamycin and tauroursodeoxycholic acid studies supported that endoplasmic reticulum stress contributes to decreased taurine transporter expression in hyperoxia lungs. The effect of taurine treatment on reducing endoplasmic reticulum stress, increasing ND5 and ND6 expression, angiogenesis, and, most importantly, the alveolar formation is beneficial to hyperoxia rat pups. Conclusion: Hyperoxia exposure causes endoplasmic reticulum stress, increases taurine transporter degradation, and leads to taurine depletion in the neonatal lungs with subsequent metabolic dysregulation, resulting in poor alveolar formation of the neonatal lungs. We provide evidence of the never-being-reported protective role of taurine in neonatal lung development. The fact that taurine attenuates the severity of bronchopulmonary dysplasia by reducing hyperoxia-induced endoplasmic reticulum stress and mitochondrial dysfunction indicates its therapeutic potential for treating bronchopulmonary dysplasia. Sprague-Dawley rat pups exposed to >90% oxygen (hyperoxia) were used as the bronchopulmonary dysplasia phenotype between postnatal days one and ten. Some rat pups received tunicamycin or tauroursodeoxycholic acid to study the effect of endoplasmic reticulum stress. Taurine was used as rescue therapy. Plasma and lungs were obtained at postnatal day ten for multiomics analyses. The dam and pups were cared for in either >90% oxygen chamber (HOX) or room air (NOX) from postnatal day 1 to day 10 (P1-P10). An oxygen sensor continuously monitored oxygen concentrations (Reming Bioinstruments Co., Redfield, NY). Pups were then recovered in room air between P11-P21. Pups were caged with nursing dams while the dams were alternated between oxygen environments to diminish oxygen toxicity. Lungs obtained at P21 from both NOX and HOX groups were used for transcriptomic studies using Affymetrix chips, histology, and immunoblots.