Department of Medical Science and Technology, Hiroshima International University, Higashi-hiroshima, Hiroshima 739-2695, Japan.
Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu 501-1196, Japan.
Molecules. 2020 Dec 28;26(1):90. doi: 10.3390/molecules26010090.
Ferulic Acid (FA) is a highly abundant phenolic phytochemical which is present in plant tissues. FA has biological effects on physiological and pathological processes due to its anti-apoptotic and anti-oxidative properties, however, the detailed mechanism(s) of function is poorly understood. We have identified FA as a molecule that inhibits apoptosis induced by hydrogen peroxide (HO) or actinomycin D (ActD) in rat pheochromocytoma, PC12 cell. We also found that FA reduces HO-induced reactive oxygen species (ROS) production in PC12 cell, thereby acting as an anti-oxidant. Then, we analyzed FA-mediated signaling responses in rat pheochromocytoma, PC12 cells using antibody arrays for phosphokinase and apoptosis related proteins. This FA signaling pathway in PC12 cells includes inactivation of pro-apoptotic proteins, SMAC/Diablo and Bad. In addition, FA attenuates the cell injury by HO through the inhibition of phosphorylation of the extracellular signal-regulated kinase (ERK). Importantly, we find that FA restores expression levels of brain-derived neurotrophic factor (BDNF), a key neuroprotective effector, in HO-treated PC12 cells. As a possible mechanism, FA increases BDNF by regulating microRNA-10b expression following HO stimulation. Taken together, FA has broad biological effects as a neuroprotective modulator to regulate the expression of phosphokinases, apoptosis-related proteins and microRNAs against oxidative stress in PC12 cells.
阿魏酸（FA）是一种在植物组织中含量丰富的酚类植物化学物质。由于其抗细胞凋亡和抗氧化特性，FA 对生理和病理过程具有生物学效应，但其功能的详细机制尚不清楚。我们已经确定 FA 是一种能够抑制过氧化氢（HO）或放线菌素 D（ActD）诱导的大鼠嗜铬细胞瘤 PC12 细胞凋亡的分子。我们还发现 FA 减少了 HO 诱导的 PC12 细胞中活性氧（ROS）的产生，从而起到抗氧化作用。然后，我们使用磷酸激酶和凋亡相关蛋白的抗体阵列分析 FA 介导的大鼠嗜铬细胞瘤 PC12 细胞中的信号反应。该 FA 信号通路包括抑制促凋亡蛋白 SMAC/Diablo 和 Bad 的失活。此外，FA 通过抑制细胞外信号调节激酶（ERK）的磷酸化来减轻 HO 引起的细胞损伤。重要的是，我们发现 FA 通过调节 HO 刺激后 microRNA-10b 的表达来恢复 HO 处理的 PC12 细胞中脑源性神经营养因子（BDNF）的表达水平。作为一种可能的机制，FA 通过调节 microRNA-10b 的表达增加 BDNF，从而在 PC12 细胞中对抗氧化应激调节磷酸激酶、凋亡相关蛋白和 microRNAs 的表达。
