Valproic acid sodium salt (Sodium Valproate) is the sodium salt form of valproic acid with anti-epileptic activity. Valproic acid sodium salt is converted into its active form, valproate ion, in blood. Although the mechanism of action remains to be elucidated, Valproic acid sodium salt increases concentrations of gamma-aminobutyric acid (GABA) in the brain, probably due to inhibition of the enzymes responsible for the catabolism of GABA. This potentiates the synaptic actions of GABA. Valproic acid sodium salt may also affect potassium channels, thereby creating a direct membrane-stabilizing effect.

HDAC1:0.4 mM

在MT-450大鼠乳腺癌模型中,Valproic acid对原发肿瘤的生长具有延迟作用.

在培养的细胞中,Valproic acid与组蛋白去乙酰化酶抑制剂曲古抑菌素A一样可引起组蛋白去乙酰化。Valproic acid,如曲古抑菌素 A,也激活不同的外源性和内源性启动子的转录。在脊椎动物的胚胎中,Valproic acid和曲古抑菌素A的致畸作用非常相似,却不激活转录。 通过不同的途径Valproic acid可直接抑制组蛋白脱乙酰基酶,对HDAC1的IC50为0.4 mM。在F9和P19畸胎瘤细胞中,Valproic acid抑制细胞增殖或存活,表现为[3H]胸苷渗入下降。Valproic acid还促进啮齿动物肝脏过氧化物酶体增殖。在表达糖皮质激素受体的DNA结合域和PPARδ的配体结合结构域,以及GR控制的报告基因融合的细胞中,Valproic acid（1 mM）抑制与N-COR,TR或PPARδ融合的Gal4释放。Valproic acid诱导乙酰化组蛋白积累的减少并抑制HDAC活性。Valproic acid诱导特定类型分化,标志是增殖减少,形态改变,AP-2的转录因子累积和标志物基因表达,AP-2是神经元或神经嵴细胞样分化的F9畸胎瘤细胞的潜在标记物。

The activity of caspase-3, -8 and -9 is assessed using the caspase-3, -8 and -9 colorimetric assay kits, respectively. In brief, 1×106?cells in a 60-mm culture dish are incubated with 10 mM Valproic acid for 24 h. The cells are then washed in PBS and suspended in 5 volumes of lysis buffer provided with the kit. Protein concentrations are determined using the Bradford method. Supernatants containing 50 μg total protein are used to determine caspase-3, -8 and -9 activities. The supernatants are added to each well in 96-well microtiter plates with DEVD-pNA, IETD-pNA or LEHD-pNA as caspase-3, -8 and -9 substrates and the plates are incubated at 37°C for 1 h. The optical density of each well is measured at 405 nm using a microplate reader. The activity of caspase-3, -8 and -9 is expressed in arbitrary absorbance units.

Valproic acid is dissolved in DMSO. In brief, 5×105?cells are seeded in 96-well microtiter plates for MTT assays. After exposure to the designated doses of Valproic acid for the indicated times, MTT solution [20 mL: 2 mg/mL in phosphate-buffered saline (PBS)] is added to each well of the 96-well plates. The plates are additionally incubated for 3 h at 37°C. Medium is withdrawn from the plates by pipetting and 200 mL DMSO is added to each well to solubilize the formazan crystals. The optical density is measured at 570 nm using a microplate reader.