Harada Tomoya, Yamasaki Akira, Chikumi Hiroki, Hashimoto Kiyoshi, Okazaki Ryota, Takata Miki, Fukushima Takehito, Watanabe Masanari, Kurai Jun, Halayko Andrew J, Shimizu Eiji
Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
Pulm Pharmacol Ther. 2015 Jun;32:45-52. doi: 10.1016/j.pupt.2015.04.003. Epub 2015 May 6.
Vitamin E is an antioxidant that occurs in 8 different forms (α, β, γ, and δ tocopherol and tocotrienol). Clinical trials of tocopherol supplementation to assess the impact of antioxidant activity in asthma have yielded equivocal results. Tocotrienol exhibits greater antioxidant activity than tocopherol in several biological phenomena in vivo and in vitro. We tested the effect of tocotrienol on human airway smooth muscle (ASM) cell growth and migration, both of which mediate airway remodeling in asthma.
We measured platelet-derived growth factor-BB (PDGF-BB)-induced ASM cell proliferation and migration by colorimetric and Transwell migration assays in the presence and absence of γ-tocotrienol (an isoform of tocotrienol).
PDGF-BB-induced ASM cell proliferation and migration were inhibited by γ-tocotrienol. This effect was associated with inhibition of RhoA activation, but it had no effect on p42/p44 mitogen-activated protein kinase (MAPK) or Akt1 activation. We confirmed that pharmacological inhibition of Rho kinase activity was sufficient to inhibit PDGF-BB-induced ASM cell proliferation and migration.
γ-Tocotrienol could impart therapeutic benefits for airway remodeling in asthma by inhibiting human ASM cell proliferation and migration.
维生素E是一种抗氧化剂,有8种不同形式(α、β、γ和δ生育酚及生育三烯酚)。补充生育酚以评估抗氧化活性对哮喘影响的临床试验结果不一。在体内和体外的多种生物学现象中,生育三烯酚比生育酚表现出更强的抗氧化活性。我们测试了生育三烯酚对人气道平滑肌(ASM)细胞生长和迁移的影响,这两者均介导哮喘中的气道重塑。
我们在有和没有γ-生育三烯酚(生育三烯酚的一种异构体)存在的情况下,通过比色法和Transwell迁移试验测量血小板衍生生长因子-BB(PDGF-BB)诱导的ASM细胞增殖和迁移。
γ-生育三烯酚抑制了PDGF-BB诱导的ASM细胞增殖和迁移。这种作用与RhoA激活的抑制有关,但对p42/p44丝裂原活化蛋白激酶(MAPK)或Akt1激活没有影响。我们证实,Rho激酶活性的药理学抑制足以抑制PDGF-BB诱导的ASM细胞增殖和迁移。
γ-生育三烯酚可通过抑制人ASM细胞增殖和迁移为哮喘气道重塑带来治疗益处。