Tsuneyoshi Tadamitsu
Central Research Institute, Wakunaga Pharmaceutical Co. Ltd., Akitakata, Hiroshima 739-1195, Japan.
Exp Ther Med. 2020 Feb;19(2):1500-1503. doi: 10.3892/etm.2019.8380. Epub 2019 Dec 27.
In clinical studies, aged garlic extract (AGE) has been shown to improve endothelial dysfunction. The activation of nuclear factor erythroid 2 like 2 (Nrf2)-dependent gene expression is a proposed mechanism for maintaining vascular homeostasis. -1-propenylcysteine (S1PC) and -allylcysteine (SAC) are two predominant sulfur-containing amino acids present in AGE. However, it remains unclear as to whether the two sulfur amino acids activate Nrf2 in cells. Nitric oxide (NO) is an important signaling molecule and one of the activators of the Nrf2 pathway. In a previous study, we examined the effects of the two sulfur amino acids on NO signaling for modulating the Nrf2-dependent antioxidant response. Neither S1PC nor SAC were found to affect the expression of Nrf2-regulated genes, such as heme oxygenase-1 () in human umbilical vein endothelial cells. However, S1PC was found to augment expression, induced by NO donors, such as NOR3. NOR3 was found to induce the nuclear accumulation of NRF2 protein and concomitantly enhance the degradation of BTB domain and CNC homolog 1 (BACH1), a transcriptional repressor that competes with NRF2. Notably, on our previous study, S1PC enhanced the NOR3-induced downregulation of BACH1, but did not further enhance the NOR3-induced accumulation of NRF2. The findings of that study indicated that the S1PC-induced degradation of BACH1 may provide a basis for the antioxidant effects of AGE. Thus, in this review, we aimed to provide a current overview of the antioxidant effects of AGE and sulfur-containing amino acids.
在临床研究中，已证明 aged garlic extract（AGE，蒜氨酸）可改善内皮功能障碍。核因子红细胞 2 相关因子 2（Nrf2）依赖性基因表达的激活是维持血管稳态的一种推测机制。S-1-丙烯基半胱氨酸（S1PC）和 S-烯丙基半胱氨酸（SAC）是 AGE 中存在的两种主要含硫氨基酸。然而，这两种含硫氨基酸是否在细胞中激活 Nrf2 仍不清楚。一氧化氮（NO）是一种重要的信号分子，也是 Nrf2 途径的激活剂之一。在先前的一项研究中，我们研究了这两种含硫氨基酸对 NO 信号传导的影响，以调节 Nrf2 依赖性抗氧化反应。在人脐静脉内皮细胞中，未发现 S1PC 和 SAC 影响 Nrf2 调节基因的表达，如血红素加氧酶-1（）。然而，发现 S1PC 可增强由 NO 供体如 NOR3 诱导的 表达。发现 NOR3 诱导 NRF2 蛋白的核积累，并同时增强与 NRF2 竞争的转录抑制因子 BTB 结构域和 CNC 同源物 1（BACH1）的降解。值得注意的是，在我们先前的研究中，S1PC 增强了 NOR3 诱导的 BACH1 下调，但并未进一步增强 NOR3 诱导的 NRF2 积累。该研究结果表明，S1PC 诱导的 BACH1 降解可能为 AGE 的抗氧化作用提供基础。因此，在本综述中，我们旨在提供 AGE 和含硫氨基酸抗氧化作用的当前概述。
