title: The effect of ferulic acid ethyl ester on leptin-induced proliferation and migration of aortic smooth muscle cells.
abstract: Leptin is a peptide hormone, which has a central role in the regulation of body weight; it also exerts many potentially atherogenic effects. Ferulic acid ethyl ester (FAEE) has been approved for antioxidant properties. The aim of this study was to investigate whether FAEE can inhibit the atherogenic effects of leptin and the possible molecular mechanism of its action. Both of cell proliferation and migration were measured when the aortic smooth muscle cell (A10 cell) treated with leptin and/or FAEE. Phosphorylated p44/42MAPK, cell cycle-regulatory protein (for example, cyclin D1, p21, p27), β-catenin and matrix metalloproteinase-9 (MMP-9) proteins levels were also measured. Results demonstrated that leptin (10, 100 ng ml(-1)) significantly increased the proliferation of cells and the phosphorylation of p44/42MAPK in A10 cells. The proliferative effect of leptin was significantly reduced by the pretreatment of U0126 (0.5 μM), a MEK inhibitor, in A10 cells. Meanwhile, leptin significantly increased the protein expression of cyclin D1, p21, β-catenin and decreased the expression of p27 in A10 cells. In addition, leptin (10 ng ml(-1)) significantly increased the migration of A10 cells and the expression of MMP-9 protein. Above effects of leptin were significantly reduced by the pretreatment of FAEE (1 and 10 μM) in A10 cells. In conclusion, FAEE exerts multiple effects on leptin-induced cell proliferation and migration, including the inhibition of p44/42MAPK phosphorylation, cell cycle-regulatory proteins and MMP-9, thereby suggesting that FAEE may be a possible therapeutic approach to the inhibition of obese vascular disease.
authors: Department of Obstetrics and Gynecology, Chi-Mei Medical Center, Tainan, Taiwan.|Department of Medicine, Taipei Medical University, Taipei, Taiwan.|Department of Sport Management, Chia Nan University of Pharmacy and Science, Tainan, Taiwan.
authors: Yung-Chieh
authors: YC
authors: Tsai
authors: Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan.
authors: Yen-Mei
authors: YM
authors: Lee
authors: Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors: Chih-Hsiung
authors: CH
authors: Hsu
authors: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors: Sy-Ying
authors: SY
authors: Leu
authors: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
authors: Hsiao-Yen
authors: HY
authors: Chiang
authors: Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan.
authors: Mao-Hsiung
authors: MH
authors: Yen
authors: Department of Physiology and Biophysics; Graduate Institute of Physiology, National Defense Medical Center, Taipei, Taiwan.
authors: Pao-Yun
authors: PY
authors: Cheng
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000166:cytology / Q000187:drug effects*; D002109:Caffeic Acids / Q000494:pharmacology*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D020738:Leptin / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002109:Caffeic Acids; D020738:Leptin; D051176:beta Catenin; C099085:ethyl ferulate; D020780:Matrix Metalloproteinase 9