Ferulate, an Active Component of Wheat Germ, Ameliorates Oxidative Stress-Induced PTK/PTP Imbalance and PP2A Inactivation
Toxicol. Res. 2018;34:333−341
Published online October 15, 2018;  https://doi.org/10.5487/TR.2018.34.4.333
© 2018 Korean Society of Toxicology.

Eun Mi Koh1,†, Eun Kyeong Lee1,†, Chi Hun Song1, Jeongah Song2, Hae Young Chung3, Chang Hoon Chae4 and Kyung Jin Jung1,5

1Bioanalytical and Immunoanalytical Research Group, Korea Institute of Toxicology, Daejeon, Korea
2Animal Model Research Center, Korea Institute of Toxicology, Jeonbuk, Korea
3Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan, Korea
4Celldi, 2-212 Jeonbuk TechnoPark, Wanju, Korea
5Department of Human and Environmental Toxicology, Korea University of Science and Technology (UST), Daejeon, Korea
Kyung Jin Jung, Bioanalytical and Immunoanalytical Research Group, Analytical Research Center, Korea Institute of Toxicology, 141 Gajungro, Yuseong-gu, Daejeon 34114, Korea
E-mail: jungk@kitox.re.kr
The first two authors contributed equally to this work.
Received: August 25, 2017; Revised: June 4, 2018; Accepted: July 4, 2018
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ferulate is a phenolic compound abundant in wheat germ and bran and has been investigated for its beneficial activities. The aim of the present study is to evaluate the efficacy of ferulate against the oxidative stress-induced imbalance of protein tyrosine kinases (PTKs), protein tyrosine phosphatases (PTPs), and serine/threonine protein phosphatase 2A (PP2A), in connection with our previous finding that oxidative stress-induced imbalance of PTKs and PTPs is linked with proinflammatory nuclear factor-kappa B (NF-κB) activation. To test the effects of ferulate on this process, we utilized two oxidative stress-induced inflammatory models. First, YPEN-1 cells were pretreated with ferulate for 1 hr prior to the administration of 2,2'-Azobis(2-methylpropionamidine) dihydrochloride (AAPH). Second, 20-month-old Sprague-Dawley rats were fed ferulate for 10 days. After ferulate treatment, the activities of PTKs, PTPs, and PP2A were measured because these proteins either directly or indirectly promote NF-κB activation. Our results revealed that in YPEN-1 cells, ferulate effectively suppressed AAPH-induced increases in reactive oxygen species (ROS) and NF-κB activity, as well as AAPH-induced PTK activation. Furthermore, ferulate also inhibited AAPH-induced PTP and PP2A inactivation. In the aged kidney model, ferulate suppressed aging-induced activation of PTKs and ameliorated aging-induced inactivation of PTPs and PP2A. Thus, herein we demonstrated that ferulate could modulate PTK/PTP balance against oxidative stress-induced inactivation of PTPs and PP2A, which is closely linked with NF-κB activation. Based on these results, the ability of ferulate to modulate oxidative stress-related inflammatory processes is established, which suggests that this compound could act as a novel therapeutic agent.
Keywords : Ferulate, Wheat germ, Oxidative stress, PTK, PTP, PP2A


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