606 - Taurine Protects Hyperoxic (HOX) Neonatal Lungs Through Mitigating Endoplasmic Reticulum (ER) Stress

Poster Number: 606
Publication Number: 606.1147

Background: We previously showed that increased ER stress and impaired mitochondrial electron transport chain (ETC) activity contribute to HOX-induced alveolar simplification in rat pup lungs. One of the mechanisms is the decreased taurine transporter (TauT) stability secondary to ER stress-associated degradation. Taurine depletion from TauT degradation causes a reduced formation of two complex-1 (C1) core proteins – ND5 and ND6 – that uncouples C1 activity. While daily taurine treatment attenuates the alveolar simplification of HOX neonatal lung, the mechanism for this protection was not explored.

Objective: To investigate if taurine treatment can protect neonatal lungs under HOX without toxicity.

Design/Methods: Sprague-Dawley rat pups were raised in 21% (N) or >90% oxygen (H) with alternating nursing dams daily between P1 and P10. Taurine (100 mg/kg/d, T) was given i.p. to half of the pups as the rescue therapy, while PBS (P) was the control carrier. Lung and serum at P10 were snap-frozen for targeted metabolomics, transcriptomics (Affymetrix), and immunoblots. Lung histology was used for morphometrics. GSEA and g:Profiler and were used to analyze the transcriptomic data.

Results: Although HOX decreased lung TauT expression, taurine treatment increased [1] the blood level and lung taurine content (NP: 0.82±0.21 x 106 IS; HP: 0.41±0.09 x 106 IS; HT: 2.08±0.93 x 106 IS); [2] ND5 (~2-fold) and ND6 (~1.8-fold) expressions; and [3] TauT expression (~1.75-fold). ER stress markers (p-PERK, p-IRE1a, ATF6, and CHOP) increased in HOX lung lysates were all successfully decreased by taurine treatment. The increased expression of glycolytic enzymes (hexokinase-2, LDHA, G6PD, and PFKFB3) and glucose transporter-1 in HOX lungs were also decreased by taurine treatment. At the same time, the increased expression of representative subunits for each ETC protein also decreased. Although the taurine treatment did not affect the mortality rate and weight gain, the alveolar complexity improved in the HOX lungs.

Conclusion(s): Taurine does increase the lung taurine content and improves the oxidative phosphorylation in the HOX lungs by reducing ER stress and correcting the deranged glucose metabolism.