γ-氨基丁酸(GABA)具有广泛的生理功能,可以直接从食品中获得。已经开发了富含GABA的功能性食品,并且对GABA的商业需求正在增加。GABA是一种公认的中枢神经系统抑制性神经递质,通过与其受体结合在某些疾病中发挥重要作用。然而,GABA的某些功能不能通过神经传递或GABA受体途径来解释。因此,这项研究调查了GABA是否具有抑制组蛋白去乙酰化酶(HDAC)的潜力。
发现GABA在SH-SY5Y细胞(表达GABA受体)中抑制HDAC1/2/3表达并上调组蛋白乙酰化水平(Ace-H3K9/Ace-H4K12),3T3-L1细胞(不表达GABA受体),和老鼠的大脑皮层。谷氨酸受体2(GluR2)是α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯(AMPA)受体的亚基,与某些神经系统疾病的发病机理有关。还发现GABA通过抑制HDAC1/2而不是HDAC3来增加GluR2表达。
证明了GABA作为HDAC抑制剂的新作用。本研究拓展了探索GABA非神经递质功能的视野。
γ-Aminobutyric acid (GABA) possesses extensive physiological functions and can be directly obtained from foods. GABA-enriched functional foods have been developed and the commercial demands for GABA are increasing. GABA is widely recognized as a central nervous system inhibitory neurotransmitter and plays an important role in some diseases by binding to its receptors. However, some of the functions of GABA are not explained by neurotransmission or GABA receptor pathways. Therefore, this
study investigates whether GABA has the potential to inhibit histone deacetylase (HDAC).
It is found that GABA inhibits HDAC1/2/3 expression and upregulates histone acetylation levels (Ace-H3K9/Ace-H4K12) in SH-SY5Y cells (which express GABA receptors), 3T3-L1 cells (which do not express GABA receptors), and the cerebral cortex in mice. Glutamate receptor 2 (GluR2) is a subunit of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor and is implicated in the pathogenesis of some neurological diseases. It is also found that GABA increases GluR2 expression by inhibiting HDAC1/2 but not HDAC3.
A novel role for GABA is demonstrated in which it acts as an HDAC inhibitor. The present
study expands the horizons for exploring the non-neurotransmitter functions of GABA.