Department of Nutrition and Food Hygiene, School of Public Health, China Medical University, Shenyang, China.
Department of Nutrition and Food Hygiene, School of Public Health, Jinzhou Medical University, Jinzhou, China.
Am J Alzheimers Dis Other Demen. 2020 Jan-Dec;35:1533317519883496. doi: 10.1177/1533317519883496. Epub 2019 Oct 24.
Tyrosine kinase receptor A (TrkA) plays an important role in the protection of cholinergic neurons in Alzheimer's disease (AD). This study was designed to investigate whether β-hydroxybutyrate (BHB), an endogenous histone deacetylase (HDAC) inhibitor, upregulates the expression of TrkA by affecting histone acetylation in SH-SY5Y cells treated with amyloid β-protein (Aβ). The results showed that BHB ameliorated the reduction of cell vitality and downregulation of TrkA expression induced by Aβ. Furthermore, BHB inhibited the upregulation of HDAC1/2/3 expression and downregulation of histone acetylation (Ace-H3K9 and Ace-H4K12) levels in Aβ-treated cells. The expression of TrkA was upregulated in HDAC1- or 3-silenced SH-SY5Y cells. However, there was no significant difference in TrkA expression between the HDAC2 knockdown and control cells. In conclusion, this study demonstrates that BHB protects against Aβ-induced neurotoxicity in SH-SY5Y cells. The underlying mechanism of the effect may be associated with the upregulation of TrkA expression by inhibiting HDAC1/3.
酪氨酸激酶受体 A（TrkA）在阿尔茨海默病（AD）中胆碱能神经元的保护中发挥重要作用。本研究旨在探讨内源性组蛋白去乙酰化酶（HDAC）抑制剂β-羟基丁酸（BHB）是否通过影响 Aβ 处理的 SH-SY5Y 细胞中的组蛋白乙酰化来上调 TrkA 的表达。结果表明，BHB 改善了 Aβ 诱导的细胞活力降低和 TrkA 表达下调。此外，BHB 抑制了 Aβ 处理细胞中 HDAC1/2/3 表达的上调和组蛋白乙酰化水平（Ace-H3K9 和 Ace-H4K12）的下调。在沉默 HDAC1 或 3 的 SH-SY5Y 细胞中，TrkA 的表达上调。然而，在 HDAC2 敲低和对照细胞之间，TrkA 的表达没有显著差异。总之，本研究表明 BHB 可防止 SH-SY5Y 细胞中 Aβ 诱导的神经毒性。其作用的潜在机制可能与抑制 HDAC1/3 上调 TrkA 表达有关。
