Supplemental oxygen alters the pentose phosphate pathway in the developing mouse brain through SIRT signaling

• Published in: Neurochemistry international 2024-11, Vol.180, p.105886, Article 105886
• Main Authors: Engur, Defne, Cilaker Micili, Serap, Soy, Sila, Bilici, Gökcen, Tufekci, Kemal Ugur, Kiser, Cagla, Ercan, İlkcan, Kumral, Abdullah, Genc, Sermin
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Brain - growth & development; Brain - metabolism; Female; Glucose - metabolism; Glucosephosphate Dehydrogenase - metabolism; Hyperoxia; Male; Mice; Mice, Inbred C57BL; Newborn; Oxygen; Oxygen - metabolism; Pentose phosphate pathway; Pentose Phosphate Pathway - drug effects; Pentose Phosphate Pathway - physiology; Signal Transduction - physiology; SIRT; Sirtuin 1 - metabolism
• ISSN: 0197-0186; 1872-9754; 1872-9754
• DOI: 10.1016/j.neuint.2024.105886

Oxygen support plays a critical role in the management of preterm infants in neonatal intensive care units. On the other hand, the possible effects of oxygen supplementation on cellular functions, specifically glucose metabolism, have been less understood. of the study is to investigate whether supplemental oxygen alters glucose metabolism and pentose phosphate pathway (PPP) activity in the brain tissue and its relevance with silent information regulator proteins (SIRT) pathway. For this purpose, newborn C57BL/6 pups were exposed to 90% oxygen from birth until postnatal day 7 (PN7) and metabolites of glysolysis and PPP were investigated through metabolomics analysis. SIRT1, glucose-6-phosphate dehydrogenase (G6PD) and transaldolase (TALDO) proteins were examined immunohistochemically and molecularly in the prefrontal and hippocampus regions of the brain. Later on, SIRT1 inhibition was carried out. Our results indicate that supplemental oxygen causes an increase in PPP metabolites as well as activation of G6PD enzyme in the brain tissue, which is reversed by SIRT1 inhibition. Our study underlines a connection between supplemental oxygen, glucose metabolism, PPP pathway and the SIRT signaling. Understanding these intricate relationships not only deepens our knowledge of cellular physiology but also holds promise for therapeutic interventions for creating neuroprotective strategies in preterm brain. •Purpose of the study is to investigate whether oxygen alters glucose metabolism and pentose phosphate pathway (PPP) in the brain.•Oxygen elevates PPP metabolites and activates G6PD enzyme in the brain which is reversed by SIRT1 inhibition.•Our study underlines a connection, between oxygen, glucose metabolism, PPP and the SIRT signaling.•Understanding these relationship holds promise for for neuroprotective strategies in preterm brain.