Tomoya Harada1, Akira Yamasaki2, Hiroki Chikumi1, Kiyoshi Hashimoto1, Ryota Okazaki1, Miki Takata1, Takehito Fukushima1, Masanari Watanabe1, Jun Kurai1, Andrew J Halayko3, Eiji Shimizu1. 1. Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan. 2. Division of Medical Oncology and Molecular Respirology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan. Electronic address: yamasaki@grape.med.tottori-u.ac.jp. 3. Department of Physiology and Internal Medicine, University of Manitoba, Winnipeg, Canada.
Abstract
AIMS: 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. MAIN METHODS: 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). KEY FINDINGS: 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. SIGNIFICANCE: γ-Tocotrienol could impart therapeutic benefits for airway remodeling in asthma by inhibiting human ASM cell proliferation and migration.
AIMS: 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. MAIN METHODS: 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). KEY FINDINGS: 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. SIGNIFICANCE: γ-Tocotrienol could impart therapeutic benefits for airway remodeling in asthma by inhibiting human ASM cell proliferation and migration.
Authors: Venkata Sita Rama Raju Allam; Keshav Raj Paudel; Gaurav Gupta; Sachin Kumar Singh; Sukriti Vishwas; Monica Gulati; Saurabh Gupta; M V N L Chaitanya; Niraj Kumar Jha; Piyush Kumar Gupta; Vyoma K Patel; Gang Liu; Mohammad Amjad Kamal; Philip M Hansbro; Brian Gregory George Oliver; Dinesh Kumar Chellappan; Kamal Dua Journal: Environ Sci Pollut Res Int Date: 2022-07-07 Impact factor: 5.190
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