Inhibitory Effects of Triphlorethol-A on MMP-1 Induced by Oxidative Stress in Human Keratinocytes via ERK and AP-1 Inhibition

Abstract

Oxidative stress is known to generate reactive oxygen species (ROS) in cells, which subsequently induce the synthesis of matrix metalloproteinases (MMP) and an aging phenomenon. The protective effects of triphlorethol-A, derived from Ecklonia cava, were investigated against hydrogen peroxide (H₂O₂)-induced damage using human skin keratinocytes. Data showed that triphlorethol-A inhibited ROS formation, induced catalase expression, inhibited DNA damage, and increased cell viability in keratinocytes. Triphlorethol-A treatment significantly reduced MMP-1 expression and production, compared to H₂O₂-treated cells. In addition, triphlorethol-A abrogated the activation of extracellular signal regulated protein kinase (ERK), which originates upstream of MMP-1 expression, and was induced by H₂O₂ treatment. Moreover, triphlorethol-A inhibited DNA binding activity of activator protein-1 (AP-1), a downstream transcription factor of ERK. Data indicate that the antioxidative properties of triphlorethol-A involve the inhibition of MMP-1 via ERK and AP-1 inhibition.

Acknowledgments

This study was supported by a grant (IH-9–12–10018193) from the Korea Ministry of Commerce, Industry, and Energy and by the program of Basic Atomic Energy Research Institute (BAERI), which is a part of the Nuclear R&D programs grant from the Ministry of Science and Technology of Korea.