title: Spermidine inhibits MMP-2 via modulation of histone acetyltransferase and histone deacetylase in HDFs.
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.
authors.affiliation: Department of Chemistry, Dong-Eui University, Busan 614-714, Republic of Korea.
authors.forename: In-Hwan
authors.initials: IH
authors.lastname: Park
authors.forename: Moon-Moo
authors.initials: MM
authors.lastname: Kim
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics; D012867:Skin / Q000166:cytology; D013095:Spermidine / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D019715:Tissue Inhibitor of Metalloproteinase-1; D051548:Histone Acetyltransferases; D020928:Mitogen-Activated Protein Kinases; D020778:Matrix Metalloproteinase 2; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D006655:Histone Deacetylases; D013095:Spermidine