title: Protocatechuic aldehyde inhibits TNF-α-induced fibronectin expression in human umbilical vein endothelial cells via a c-Jun N-terminal kinase dependent pathway.
abstract: Fibronectin (FN) is one of the most important extracellular matrix proteins and plays an important role in the pathogenesis of atherosclerosis (AS). The aim of the present study was to evaluate the effect of a potent, water-soluble antioxidant, protocatechuic aldehyde (PA), which is derived from the Chinese herbSalvia miltiorrhiza, on the expression of FN in human umbilical vein endothelial cells (HUVECs) stimulated with tumor necrosis factor-α (TNF-α). The pharmacological effects of PA on the production of FN were investigated using ELISA and western blot analysis. In addition, ELISA and western blot analysis were used to examine the activation and suppression of the mitogen-activated protein kinase (MAPK) pathways and nuclear factor (NF)-κB in TNF-α-stimulated HUVECs, in order to explore the underlying pharmacological mechanism of PA. The inhibitory effect of PA on the total generation of reactive oxygen species (ROS) in TNF-α-stimulated HUVECs was assessed using 2',7'-dichlorofluorescein diacetate. Pretreatment of HUVECs with PA (0.15, 0.45 and 1.35 mM) for 18 h markedly attenuated the TNF-α-stimulated FN surface expression and secretion in a dose-dependent manner. Intracellular ROS generation and the expression of extracellular signal-regulated kinase 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 MAPK (p38) were significantly induced by TNF-α (2 ng/ml) in HUVECs. TNF-α-induced ROS generation and JNK activation were inhibited by PA in a concentration-dependent manner. By contrast, ERK1/2 and p38 activation was not significantly affected by PA. Pretreatment of HUVECs with PA for 18 h markedly attenuated TNF-α-stimulated NF-κB activation. In conclusion, the present findings suggest that PA inhibits TNF-α-induced FN expression in HUVECs through a mechanism that involves ROS/JNK and NF-κB.
authors.affiliation: Division of Cardiology, The First Yongkang Municipal Hospital, Yongkang, Zhejiang 321300, P.R. China.
authors.forename: Yue-Feng
authors.initials: YF
authors.lastname: Tong
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Division of Cardiology, The First Yongkang Municipal Hospital, Yongkang, Zhejiang 321300, P.R. China.
authors.forename: Zhi-Xing
authors.initials: ZX
authors.lastname: Hu
authors.affiliation: Division of Cardiology, The First Yongkang Municipal Hospital, Yongkang, Zhejiang 321300, P.R. China.
authors.forename: Zhe-Cheng
authors.initials: ZC
authors.lastname: Li
authors.affiliation: Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China.
authors.forename: Agula
authors.initials: A
authors.lastname: A
keywords: endothelial cell; fibronectin; mitogen-activated protein kinase; protocatechuic aldehyde; tumor necrosis factor-α