Table_9_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功能产生负面影响。蛋白质乙酰化（protein acetylation）是一种广泛存在的蛋白质修饰方式，在突触可塑性（synaptic plasticity）和认知过程中发挥关键作用。然而，慢性间歇性缺氧诱导的海马整体蛋白质乙酰化及其对海马功能与行为的具体影响仍有待深入阐明。
方法
为填补这一研究空白，本研究采用液相色谱-串联质谱（liquid chromatography-tandem mass spectrometry），对暴露于间歇性缺氧4周（构建慢性间歇性缺氧模型）的健康成年小鼠海马的赖氨酸乙酰化组（lysine acetylome）与蛋白质组（proteome）进行分析，并以常氧小鼠作为对照。
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，其表达紊乱主要集中于氧化磷酸化（oxidative phosphorylation）、三羧酸（TCA）循环以及糖酵解，上述通路均仅定位于线粒体。此外，我们观察到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障碍相关。
讨论
本研究有助于阐明慢性间歇性缺氧诱导的海马蛋白质乙酰化变化的分子机制。通过为慢性间歇性缺氧相关的病理生理过程及其对海马功能的影响提供有价值的见解，我们的研究结果有助于更好地理解慢性间歇性缺氧诱导的海马蛋白质乙酰化变化的后果，以及慢性间歇性缺氧在认知功能障碍中的潜在作用。