Table_2_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（protein acetylation）作为一种常见的蛋白质修饰方式，在突触可塑性（synaptic plasticity）与认知过程中发挥着关键作用。然而，慢性间歇性缺氧诱导的海马体整体蛋白质乙酰化现象，及其对海马体功能与行为的具体影响，目前仍鲜为人知。
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（liquid chromatography-tandem mass spectrometry），对暴露于间歇性缺氧4周的健康成年小鼠（慢性间歇性缺氧模型组）与常氧小鼠（对照组）的海马组织赖氨酸乙酰化组（lysine acetylome）与蛋白质组（proteome）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，其紊乱主要集中于氧化磷酸化（oxidative phosphorylation）、三羧酸（tricarboxylic acid, TCA）循环以及糖酵解（glycolysis）通路，且上述通路均特异性定位于线粒体（mitochondria）。此外，本研究还观察到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损伤相关。
讨论
本研究有助于阐明慢性间歇性缺氧诱导海马体蛋白质乙酰化改变的分子机制。通过为慢性间歇性缺氧相关的病理生理过程及其对海马体功能的影响提供有价值的见解，本研究结果有助于进一步理解慢性间歇性缺氧诱导的海马体蛋白质乙酰化改变所带来的后果，以及慢性间歇性缺氧在认知损伤中潜在的作用。