Table_7_Acetylome analyses provide novel insights into the effects of chronic intermittent hypoxia on hippocampus-dependent cognitive impairment.xlsx

IntroductionChronic intermittent hypoxia (CIH) can negatively affect hippocampal function through various molecular mechanisms. Protein acetylation, a frequently occurring modification, plays crucial roles in synaptic plasticity and cognitive processes. However, the global protein acetylation induced by CIH in the hippocampus and its specific effects on hippocampal function and behavior remain poorly understood.
MethodsTo address this gap, we conducted a study using liquid chromatography-tandem mass spectrometry to analyze the lysine acetylome and proteome of the hippocampus in healthy adult mice exposed to intermittent hypoxia for 4 weeks (as a CIH model) compared to normoxic mice (as a control).
ResultsWe identified and quantified a total of 2,184 lysine acetylation sites in 1,007 proteins. Analysis of these acetylated proteins revealed disturbances primarily in oxidative phosphorylation, the tricarboxylic acid (TCA) cycle, and glycolysis, all of which are localized exclusively to mitochondria. Additionally, we observed significant changes in the abundance of 21 proteins, some of which are known to be associated with cognitive impairments.
DiscussionThis study helps to elucidate the molecular mechanisms underlying CIH-induced changes in protein acetylation in the hippocampus. By providing valuable insights into the pathophysiological processes associated with CIH and their impacts on hippocampal function, our findings contribute to a better understanding of the consequences of CIH-induced changes in protein acetylation in the hippocampus and the potential role of CIH in cognitive impairment.

引言
慢性间歇性缺氧（Chronic Intermittent Hypoxia，CIH）可通过多种分子机制对海马体功能产生负面影响。蛋白质乙酰化作为一种普遍存在的修饰方式，在突触可塑性与认知过程中发挥关键作用。然而，CIH诱导的海马体整体蛋白质乙酰化修饰，及其对海马体功能与行为的具体影响，目前仍知之甚少。
方法
为填补这一研究空白，本研究采用液相色谱-串联质谱法，对暴露于间歇性缺氧环境4周的健康成年小鼠（作为CIH模型）与常氧对照小鼠的海马体赖氨酸乙酰化组与蛋白质组进行分析。
结果
本研究共在1007个蛋白质中鉴定并定量到2184个赖氨酸乙酰化位点。对这些乙酰化蛋白质的分析显示，其功能紊乱主要集中于氧化磷酸化、三羧酸（TCA）循环与糖酵解通路，且这些通路均仅定位于线粒体。此外，本研究观察到21个蛋白质的丰度发生显著变化，其中部分蛋白质已被证实与认知功能损伤相关。
讨论
本研究有助于阐明CIH诱导的海马体蛋白质乙酰化修饰改变的分子机制。本研究为解析与CIH相关的病理生理过程及其对海马体功能的影响提供了宝贵见解，研究结果有助于进一步理解CIH诱导的海马体蛋白质乙酰化修饰改变所带来的后果，以及CIH在认知功能损伤中潜在的作用。