Spermidine inhibits MMP-2 via modulation of histone acetyltransferase and histone deacetylase in HDFs

Int J Biol Macromol. 2012 Dec;51(5):1003-7. doi: 10.1016/j.ijbiomac.2012.08.013. Epub 2012 Aug 25.

Abstract

In recent years, aging has been reported to be regulated by HAT. In this study, the inhibitory effects of spermidine on the matrix metalloproteinase-2 (MMP-2) activity and expression were investigated in human dermal fibroblasts (HDFs). It was observed that spermidine inhibits MMP-2 activity and expression. In addition, the expression levels of histone acetyltransferase (HAT), phospho-extracellular-signal related kinase (p-ERK), phospho-c-jun N-terminal kinase (p-JNK), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) are decreased in the presence of spermidine. In contrast, the expression levels of histone deacetylase 1 (HDAC1), sirtuin 1 (SIRT1), phospho-p38 (p-p38) are increased by spermidine. In conclusion, our results suggest that spermidine could have a therapeutic potential in inhibition of metastasis through the inhibitory effects on activity and expression of MMP-2 via regulation of HAT and HDAC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival / drug effects
  • Fibroblasts / drug effects
  • Fibroblasts / enzymology
  • Fibroblasts / metabolism
  • Gene Expression Regulation, Enzymologic / drug effects
  • Histone Acetyltransferases / metabolism*
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Humans
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism*
  • Matrix Metalloproteinase Inhibitors / pharmacology*
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / metabolism
  • Sirtuin 1 / genetics
  • Skin / cytology
  • Spermidine / pharmacology*
  • Tissue Inhibitor of Metalloproteinase-1 / genetics

Substances

  • Matrix Metalloproteinase Inhibitors
  • NF-kappa B
  • Tissue Inhibitor of Metalloproteinase-1
  • Histone Acetyltransferases
  • Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 2
  • SIRT1 protein, human
  • Sirtuin 1
  • Histone Deacetylases
  • Spermidine