Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, 100020, China.
Department of Internal Medicine, Affiliated Children Hospital of Capital Institute of Pediatrics, Beijing, 100020, China.
J Mol Neurosci. 2024 Apr 3;74(2):34. doi: 10.1007/s12031-024-02215-5.
Protein acetylation, which is dynamically maintained by histone acetyltransferases (HATs) and deacetylases (HDACs), might play essential roles in hippocampal exercise physiology. However, whether HATs/HDACs are imbalanced during the recovery phase following acute exercise has not been determined. Groups of exercised mice with different recovery periods after acute exercise (0 h, 0.5 h, 1 h, 4 h, 7 h, and 24 h) were constructed, and a group of sham-exercised mice was used as the control. The mRNA levels of HATs and HDACs were detected via real-time quantitative polymerase chain reaction. Lysine acetylation on the total proteins and some specific locations on histones were detected via western blotting, as were various acylation modifications on the total proteins. Except for four unaffected genes (Hdac4, Ncoa1, Ncoa2, and Sirt1), the mRNA expression trajectories of 21 other HATs or HDACs affected by exercise could be categorized into three clusters. The genes in Cluster 1 increased quickly following exercise, with a peak at 0.5 h and/or 1 h, and remained at high levels until 24 h. Cluster 2 genes presented a gradual increase with a delayed peak at 4 h or 7 h postexercise before returning to baseline. The expression of Cluster 3 genes decreased at 0.5 h and/or 1 h, with some returning to overexpression (Hdac1 and Sirt3). Although most HATs were upregulated and half of the affected HDACs were downregulated at 0.5 h postexercise, the global or residue-specific histone acetylation levels were unchanged. In contrast, the levels of several metabolism-related acylation products of total proteins, including acetylation, succinylation, 2-hydroxyisobutyryllysine, β-hydroxybutyryllysine, and lactylation, decreased and mainly occurred on nonhistones immediately after exercise. During the 24-h recovery phase after acute exercise, the transcriptional trajectory of HATs or the same class of HDACs in the hippocampus exhibited heterogeneity. Although acute exercise did not affect the selected sites on histone lysine residues, it possibly incurred changes in acetylation and other acylation on nonhistone proteins.
蛋白质乙酰化作用由组蛋白乙酰转移酶（HATs）和去乙酰化酶（HDACs）动态维持，可能在海马体运动生理学中发挥重要作用。然而，在急性运动后的恢复阶段，HATs/HDACs 是否失衡尚不清楚。构建了一组具有不同急性运动后恢复时间（0 h、0.5 h、1 h、4 h、7 h 和 24 h）的运动小鼠组和一组假运动的小鼠作为对照。通过实时定量聚合酶链反应检测 HATs 和 HDACs 的 mRNA 水平。通过 Western blot 检测总蛋白上赖氨酸的乙酰化和组蛋白上一些特定位置的乙酰化，以及总蛋白上各种酰化修饰。除了 4 个不受影响的基因（Hdac4、Ncoa1、Ncoa2 和 Sirt1）外，受运动影响的 21 个其他 HATs 或 HDACs 的 mRNA 表达轨迹可分为 3 个聚类。第 1 类基因在运动后迅速增加，在 0.5 h 和/或 1 h 时达到峰值，并且在 24 h 时仍保持高水平。第 2 类基因在运动后 4 h 或 7 h 逐渐增加，然后达到峰值，然后恢复到基线。第 3 类基因在 0.5 h 和/或 1 h 时表达下降，其中一些基因的表达恢复到高水平（Hdac1 和 Sirt3）。虽然大多数 HATs 在运动后 0.5 h 时被上调，并且一半受影响的 HDACs 在运动后 0.5 h 时被下调，但总的或残基特异性组蛋白乙酰化水平没有变化。相比之下，运动后立即，几种与代谢相关的总蛋白酰化产物的水平（包括乙酰化、琥珀酰化、2-羟基异丁酰化赖氨酸、β-羟基丁酰化赖氨酸和乳酰化）降低，主要发生在非组蛋白上。在急性运动后 24 h 的恢复阶段，海马体中 HATs 或同一类 HDACs 的转录轨迹表现出异质性。虽然急性运动没有影响组蛋白赖氨酸残基上的选定位点，但它可能导致非组蛋白蛋白上的乙酰化和其他酰化发生变化。
