原儿茶酸通过调控 CD36/AMPK 通路改善内皮氧化应激。
Protocatechuic Acid-Ameliorated Endothelial Oxidative Stress through Regulating Acetylation Level via CD36/AMPK Pathway.
机构信息
College of Food Science and Engineering , Northwest A&F University , Yangling 712100 , P. R. China.
College of Biology and Food Engineering , Chongqing Three Gorges University , Chongqing 404100 , P. R. China.
出版信息
J Agric Food Chem. 2019 Jun 26;67(25):7060-7072. doi: 10.1021/acs.jafc.9b02647. Epub 2019 Jun 18.
As one of the main metabolites of anthocyanin, protocatechuic acid (PCA) possesses strong antioxidant activity. In the present study, we explored the capacity of PCA on the alleviation of endothelial oxidative stress and investigated the underlying mechanisms using RNA sequencing (RNA-Seq). In comparison with palmitic acid (PA)-treated cells, PCA (100 μM) significantly decreased the generations of 3-nitrotyrosine (3-NT) and 8-hydroxydeoxyguanosine (8-OHdG) (0.82 ± 0.01 vs 1.16 ± 0.05 and 0.80 ± 0.01 vs 1.48 ± 0.15, respectively, p < 0.01), two biomarkers of oxidative damage, and restored the levels of nitric oxide (NO) (0.97 ± 0.04 vs 0.54 ± 0.02, p < 0.01) and mitochondrial membrane potential (MMP) (0.96 ± 0.03 vs 0.86 ± 0.02, p < 0.01) in human umbilical vein endothelial cells (HUVECs). PCA also obviously reduced the level of reactive oxygen species (ROS) (0.86 ± 0.15 vs 2.67 ± 0.09, p < 0.01) in aorta from high-fat diet (HFD)-fed mice. RNA-Seq and Western blot analysis indicated that PCA markedly reduced the expression of cluster of differentiation 36 (CD36), a membrane fatty acid transporter, and reduced the generations of adenosine triphosphate (ATP) and acetyl coenzyme A (Ac-CoA). These effects of PCA were associated with decreased level of acetylated-lysine and restored the activity of manganese-dependent superoxide dismutase (MnSOD) through reducing the generation of Ac-CoA or activating Sirt1 and Sirt3 via a CD36/AMP-kinase (AMPK) dependent pathway.
作为花青素的主要代谢物之一，原儿茶酸（PCA）具有很强的抗氧化活性。在本研究中，我们使用 RNA 测序（RNA-Seq）探索了 PCA 缓解内皮氧化应激的能力，并研究了其潜在机制。与棕榈酸（PA）处理的细胞相比，PCA（100μM）显著降低了 3-硝基酪氨酸（3-NT）和 8-羟基脱氧鸟苷（8-OHdG）的生成（分别为 0.82±0.01 对 1.16±0.05 和 0.80±0.01 对 1.48±0.15，p<0.01），这两种氧化损伤的生物标志物，并恢复了人脐静脉内皮细胞（HUVEC）中一氧化氮（NO）和线粒体膜电位（MMP）的水平（分别为 0.97±0.04 对 0.54±0.02 和 0.96±0.03 对 0.86±0.02，p<0.01）。PCA 还明显降低了高脂饮食（HFD）喂养小鼠主动脉中活性氧（ROS）的水平（0.86±0.15 对 2.67±0.09，p<0.01）。RNA-Seq 和 Western blot 分析表明，PCA 显著降低了膜脂肪酸转运蛋白 CD36 的表达，并减少了三磷酸腺苷（ATP）和乙酰辅酶 A（Ac-CoA）的生成。PCA 的这些作用与乙酰化赖氨酸水平降低有关，并通过减少 Ac-CoA 的生成或通过 CD36/AMP 激酶（AMPK）依赖性途径激活 Sirt1 和 Sirt3 来恢复锰依赖性超氧化物歧化酶（MnSOD）的活性。
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