补充氧气可通过 SIRT 信号改变发育中小鼠大脑中的五糖磷酸途径

IF 4.4 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Neurochemistry international Pub Date : 2024-10-20 DOI:10.1016/j.neuint.2024.105886

Defne Engur , Serap Cilaker Micili , Sila Soy , Gökcen Bilici , Kemal Ugur Tufekci , Cagla Kiser , İlkcan Ercan , Abdullah Kumral , Sermin Genc

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引用次数: 0

摘要

氧气支持在新生儿重症监护室早产儿的管理中起着至关重要的作用。另一方面，人们对补氧对细胞功能，特别是葡萄糖代谢可能产生的影响了解较少。目的：本研究旨在探讨补充氧气是否会改变脑组织中的葡萄糖代谢和磷酸戊糖途径（PPP）活性及其与沉默信息调节蛋白（SIRT）途径的相关性。为此，新生 C57BL/6 幼崽从出生到出生后第 7 天（PN7）一直暴露在 90% 的氧气环境中，并通过代谢组学分析研究糖酵解和磷酸戊糖途径的代谢物。通过免疫组化和分子学方法检测了大脑前额叶和海马区的 SIRT1、葡萄糖-6-磷酸脱氢酶（G6PD）和转醛酸酶（TALDO）蛋白。随后进行了 SIRT1 抑制实验。我们的研究结果表明，补充氧气会导致 PPP 代谢物的增加以及脑组织中 G6PD 酶的激活，而抑制 SIRT1 则会逆转这种情况。我们的研究强调了补氧、葡萄糖代谢、PPP 途径和 SIRT 信号转导之间的联系。了解这些错综复杂的关系不仅能加深我们对细胞生理学的认识，还能为早产儿大脑神经保护策略的治疗干预带来希望。

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

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.

Purpose

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.

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来源期刊

Neurochemistry international 医学-神经科学

CiteScore

8.40

自引率

2.40%

发文量

128

审稿时长

37 days

期刊介绍： Neurochemistry International is devoted to the rapid publication of outstanding original articles and timely reviews in neurochemistry. Manuscripts on a broad range of topics will be considered, including molecular and cellular neurochemistry, neuropharmacology and genetic aspects of CNS function, neuroimmunology, metabolism as well as the neurochemistry of neurological and psychiatric disorders of the CNS.