Protocatechuic Acid Prevents oxLDL-Induced Apoptosis by Activating JNK/Nrf2 Survival Signals in Macrophages.
Protocatechuic Acid Prevents oxLDL-Induced Apoptosis by Activating JNK/Nrf2 Survival Signals in Macrophages.
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DOI：
10.1155/2015/351827
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发表时间：
2015
影响因子：
--
通讯作者：
Giovannini C
中科院分区：
文献类型：
--
作者：
Varì R;Scazzocchio B;Santangelo C;Filesi C;Galvano F;D'Archivio M;Masella R;Giovannini C
原儿茶酸（PCA）是复杂多酚的主要代谢产物之一，具有抗凋亡、抗炎和抗动脉粥样硬化等多种生物活性。氧化LDL通过损伤动脉壁细胞和诱导巨噬细胞中p53依赖性凋亡而具有致动脉粥样硬化的特性。本研究的目的是确定负责PCA对氧化低密度脂蛋白在J774 A.1巨噬细胞中产生的氧化和促凋亡损伤的保护作用的分子机制。我们发现，PCA在oxLDL处理的细胞中的存在完全抑制oxLDL诱导的p53依赖性凋亡。PCA降低oxLDL诱导的ROS过度产生，特别是防止早期ROS的增加。这种降低似乎是负责维持细胞内氧化还原稳态的主要信号，从而阻碍ROS、p38 MAPK和PKC δ诱导的p53活化。因此，促凋亡p53靶基因如p66Shc蛋白的过表达没有发生。最后，我们证明了PCA诱导JNK的激活，这反过来又决定了核Nrf2的增加，导致早期ROS过度产生的抑制。我们的结论是，PCA的抗凋亡机制最有可能与激活JNK介导的生存信号，加强细胞的抗氧化防御，而不是PCA的抗氧化能力。
Protocatechuic acid (PCA), one of the main metabolites of complex polyphenols, exerts numerous biological activities including antiapoptotic, anti-inflammatory, and antiatherosclerotic effects. Oxidised LDL have atherogenic properties by damaging arterial wall cells and inducing p53-dependent apoptosis in macrophages. This study was aimed at defining the molecular mechanism responsible for the protective effects of PCA against oxidative and proapoptotic damage exerted by oxLDL in J774 A.1 macrophages. We found that the presence of PCA in cells treated with oxLDL completely inhibited the p53-dependent apoptosis induced by oxLDL. PCA decreased oxLDL-induced ROS overproduction and in particular prevented the early increase of ROS. This decrease seemed to be the main signal responsible for maintaining the intracellular redox homeostasis hindering the activation of p53 induced by ROS, p38MAPK, and PKCδ. Consequently the overexpression of the proapoptotic p53-target genes such as p66Shc protein did not occur. Finally, we demonstrated that PCA induced the activation of JNK, which, in turn, determined the increase of nuclear Nrf2, leading to inhibition of the early ROS overproduction. We concluded that the antiapoptotic mechanism of PCA was most likely related to the activation of the JNK-mediated survival signals that strengthen the cellular antioxidant defences rather than to the PCA antioxidant power.
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影响因子：
5.6
作者：
Giovannini, Claudio;Scazzocchio, Beatrice;Masella, Roberta
通讯作者：
Masella, Roberta
影响因子：
5.2
作者：
Kay, Colin D.;Kroon, Paul A.;Cassidy, Aedin
通讯作者：
Cassidy, Aedin
影响因子：
5.3
作者：
BALL, RY;STOWERS, EC;MITCHINSON, MJ
通讯作者：
MITCHINSON, MJ
影响因子：
7.4
作者：
Gonthier, MP;Donovan, JL;Scalbert, A
通讯作者：
Scalbert, A
影响因子：
5.6
作者：
D'Archivio, Massimo;Santangelo, Carmela;Scazzocchio, Beatrice;Vari, Rosaria;Filesi, Carmela;Masella, Roberta;Giovannini, Claudio
通讯作者：
Giovannini, Claudio