Anti-angiogenic properties of coenzyme Q0 through downregulation of MMP-9/NF-κB and upregulation of HO-1 signaling in TNF-α-activated human endothelial cells

Hsin Ling Yang, Mallikarjuna Korivi, Ming Wei Lin, Ssu Ching Chen, Chih Wei Chou, You Cheng Hseu

研究成果: 雜誌貢獻期刊論文同行評審

28 引文 斯高帕斯(Scopus)

摘要

Various coenzyme Q (CoQ) analogs have been reported as anti-inflammatory and antioxidant substances. However, coenzyme Q0 (CoQ0, 2,3-dimethoxy-5-methyl-1,4-benzoquinone), a novel quinone derivative, has not been well studied for its pharmacological efficacies, and its response to cytokine stimulation remains unclear. Therefore, we investigated the potential anti-angiogenic properties of CoQ0 in human endothelial (EA.hy 926) cells against tumor necrosis factor-α (TNF-α) stimulation. We found that the non-cytotoxic concentrations of CoQ0 (2.5-10 μM) significantly suppressed the TNF-α-induced migration/invasion and tube formation abilities of endothelial cells. CoQ0 suppressed TNF-α-induced activity and protein expressions of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1) followed by an abridged adhesion of U937 leukocytes to endothelial cells. CoQ0 treatment remarkably downregulated TNF-α-induced nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB) possibly through suppressed I-κBα degradation. Furthermore, CoQ0 triggered the expressions of heme oxygenase-1 (HO-1) and γ-glutamylcysteine synthetase (γ-GCLC), followed by an increased nuclear accumulation of NF-E2 related factor-2 (Nrf2)/antioxidant response element (ARE) activity. In agreement with these, intracellular glutathione levels were significantly increased in CoQ0 treated cells. More interestingly, knockdown of HO-1 gene by specific shRNA showed diminished anti-angiogenic effects of CoQ0 against TNF-α-induced invasion, tube formation and adhesion of leukocyte to endothelial cells. Our findings reveal that CoQ0 protective effects against cytokine-stimulation are mediated through the suppression of MMP-9/NF-κB and/or activation of HO-1 signaling cascades. This novel finding emphasizes the pharmacological efficacies of CoQ0 to treat inflammation and angiogenesis.

原文???core.languages.en_GB???
頁(從 - 到)144-156
頁數13
期刊Biochemical Pharmacology
98
發行號1
DOIs
出版狀態已出版 - 1 11月 2015

指紋

深入研究「Anti-angiogenic properties of coenzyme Q0 through downregulation of MMP-9/NF-κB and upregulation of HO-1 signaling in TNF-α-activated human endothelial cells」主題。共同形成了獨特的指紋。

引用此