A naturally occurring carotenoid, lutein, reduces PDGF and H2O2 signaling and compromises migration in cultured vascular smooth muscle cells

Journal of Biomedical Science

Research

Yih-Jeng Tsai¹  Wen-Bin Wu²  Wen-Yuan Du²  Chih-Jen Tsou²  Huey-Ming Lo³ 

[1] Department of Otolaryngology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan;School of Medicine, Fu-Jen Catholic University, Taipei, Taiwan;Section of Cardiology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan;School of Medicine, Fu-Jen Catholic University, Taipei, Taiwan;

关键词: binding;    carotenoid;    lutein;    migration;    oxidative stress;    signaling;   

DOI  :  10.1186/1423-0127-19-18

 received in 2011-08-30, accepted in 2012-02-08,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundPlatelet-derived growth factor (PDGF) is a potent stimulator of growth and motility of vascular smooth muscle cells (VSMCs). Abnormalities of PDGF/PDGF receptor (PDGFR) are thought to contribute to vascular diseases and malignancy. We previously showed that a carotenoid, lycopene, can directly bind to PDGF and affect its related functions in VSMCs. In this study we examined the effect of the other naturally occurring carotenoid, lutein, on PDGF signaling and migration in VSMCs.MethodsWestern blotting was performed to examine PDGF and H2O2 signaling. Flowcytometry was used to determine PDGF binding to VSMCs. Fluorescence microscopy was performed to examine intracellular ROS production. Modified Boyden chamber system (Transwell apparatus) was used for migration assay.ResultsLutein reduced PDGF signaling, including phosphorylation of PDGFR-β and its downstream protein kinases/enzymes such as phospholipase C-γ, Akt, and mitogen-activated protein kinases (MAPKs). Although lutein possesses a similar structure to lycopene, it was striking that lutein inhibited PDGF signaling through a different way from lycopene in VSMCs. Unlike lycopene, lutein not only interacted with (bound to) PDGF but also interfered with cellular components. This was evidenced that preincubation of PDGF with lutein and treatment of VSMCs with lutein followed by removing of lutein compromised PDGF-induced signaling. Lutein reduced PDGF-induced intracellular reactive oxygen species (ROS) production and attenuated ROS- (H2O2-) induced ERK1/2 and p38 MAPK activation. A further analysis indicated lutein could inhibit a higher concentration of H2O2-induced PDGFR signaling, which is known to act through an oxidative inhibition of protein tyrosine phosphatase. Finally, we showed that lutein functionally inhibited PDGF-induced VSMC migration, whereas its stereo-isomer zeaxanthin did not, revealing a special action of lutein on VSMCs.ConclusionsOur study reveals a differential action mechanism of lutein from other reported caroteinoids and suggests a possible beneficial effect of lutein but not zeaxanthin on prevention of vascular diseases.

【 授权许可】

Unknown   
© Lo et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.