A naturally occurring carotenoid, lutein, reduces PDGF and H<sub>2</sub>O<sub>2 </sub>signaling and compromised migration in cultured vascular smooth muscle cells
<p>Abstract</p> <p>Background</p> <p>Platelet-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. W...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-02-01
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| Series: | Journal of Biomedical Science |
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| Online Access: | http://www.jbiomedsci.com/content/19/1/18 |
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| author | Lo Huey-Ming Tsai Yih-Jeng Du Wen-Yuan Tsou Chih-Jen Wu Wen-Bin |
| author_facet | Lo Huey-Ming Tsai Yih-Jeng Du Wen-Yuan Tsou Chih-Jen Wu Wen-Bin |
| author_sort | Lo Huey-Ming |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Platelet-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.</p> <p>Methods</p> <p>Western blotting was performed to examine PDGF and H<sub>2</sub>O<sub>2 </sub>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.</p> <p>Results</p> <p>Lutein 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- (H<sub>2</sub>O<sub>2</sub>-) induced ERK1/2 and p38 MAPK activation. A further analysis indicated lutein could inhibit a higher concentration of H<sub>2</sub>O<sub>2</sub>-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.</p> <p>Conclusions</p> <p>Our 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.</p> |
| first_indexed | 2024-04-13T06:34:01Z |
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| language | English |
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| spelling | doaj.art-a615e90eecf7432abe3fb29fd7c554882022-12-22T02:57:59ZengBMCJournal of Biomedical Science1021-77701423-01272012-02-011911810.1186/1423-0127-19-18A naturally occurring carotenoid, lutein, reduces PDGF and H<sub>2</sub>O<sub>2 </sub>signaling and compromised migration in cultured vascular smooth muscle cellsLo Huey-MingTsai Yih-JengDu Wen-YuanTsou Chih-JenWu Wen-Bin<p>Abstract</p> <p>Background</p> <p>Platelet-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.</p> <p>Methods</p> <p>Western blotting was performed to examine PDGF and H<sub>2</sub>O<sub>2 </sub>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.</p> <p>Results</p> <p>Lutein 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- (H<sub>2</sub>O<sub>2</sub>-) induced ERK1/2 and p38 MAPK activation. A further analysis indicated lutein could inhibit a higher concentration of H<sub>2</sub>O<sub>2</sub>-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.</p> <p>Conclusions</p> <p>Our 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.</p>http://www.jbiomedsci.com/content/19/1/18bindingcarotenoidluteinmigrationoxidative stresssignaling |
| spellingShingle | Lo Huey-Ming Tsai Yih-Jeng Du Wen-Yuan Tsou Chih-Jen Wu Wen-Bin A naturally occurring carotenoid, lutein, reduces PDGF and H<sub>2</sub>O<sub>2 </sub>signaling and compromised migration in cultured vascular smooth muscle cells Journal of Biomedical Science binding carotenoid lutein migration oxidative stress signaling |
| title | A naturally occurring carotenoid, lutein, reduces PDGF and H<sub>2</sub>O<sub>2 </sub>signaling and compromised migration in cultured vascular smooth muscle cells |
| title_full | A naturally occurring carotenoid, lutein, reduces PDGF and H<sub>2</sub>O<sub>2 </sub>signaling and compromised migration in cultured vascular smooth muscle cells |
| title_fullStr | A naturally occurring carotenoid, lutein, reduces PDGF and H<sub>2</sub>O<sub>2 </sub>signaling and compromised migration in cultured vascular smooth muscle cells |
| title_full_unstemmed | A naturally occurring carotenoid, lutein, reduces PDGF and H<sub>2</sub>O<sub>2 </sub>signaling and compromised migration in cultured vascular smooth muscle cells |
| title_short | A naturally occurring carotenoid, lutein, reduces PDGF and H<sub>2</sub>O<sub>2 </sub>signaling and compromised migration in cultured vascular smooth muscle cells |
| title_sort | naturally occurring carotenoid lutein reduces pdgf and h sub 2 sub o sub 2 sub signaling and compromised migration in cultured vascular smooth muscle cells |
| topic | binding carotenoid lutein migration oxidative stress signaling |
| url | http://www.jbiomedsci.com/content/19/1/18 |
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