Inhibitory effects of triphlorethol-A on MMP-1 induced by oxidative stress in human keratinocytes via ERK and AP-1 inhibition

J Toxicol Environ Health A. 2008;71(15):992-9. doi: 10.1080/01932690801934653.

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 (H(2)O(2))-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 H(2)O(2)-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 H(2)O(2) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Catalase / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Comet Assay
  • DNA / drug effects
  • DNA Damage
  • Enzyme Induction
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors*
  • Fluorescent Antibody Technique, Indirect
  • Free Radical Scavengers / pharmacology*
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Keratinocytes / drug effects*
  • Keratinocytes / enzymology
  • Matrix Metalloproteinase 1
  • Oxidants / pharmacology
  • Oxidative Stress
  • Phloroglucinol / analogs & derivatives*
  • Phloroglucinol / pharmacology
  • Transcription Factor AP-1 / antagonists & inhibitors*

Substances

  • Free Radical Scavengers
  • Oxidants
  • Transcription Factor AP-1
  • triphlorethol-A
  • DNA
  • Hydrogen Peroxide
  • Phloroglucinol
  • Catalase
  • Extracellular Signal-Regulated MAP Kinases
  • Matrix Metalloproteinase 1