title: Astaxanthin attenuates the UVA-induced up-regulation of matrix-metalloproteinase-1 and skin fibroblast elastase in human dermal fibroblasts.
abstract: BACKGROUND
  Repetitive exposure of the skin to UVA radiation elicits sagging more frequently than wrinkling, which is mainly attributed to its biochemical mechanism to up-regulate the expression of matrix-metalloproteinase (MMP)-1 and skin fibroblast elastase (SFE)/neutral endopeptidase (NEP), respectively.
  
  
  OBJECTIVE
  In this study, we examined the effects of a potent antioxidant, astaxanthin (AX), on the induction of MMP-1 and SFE by UVA treatment of cultured human dermal fibroblasts.
  
  
  METHODS
  Those effects were assessed by real-time RT-PCR, Western blotting and enzymic activity assays.
  
  
  RESULTS
  UVA radiation elicited a significant increase in the gene expression of MMP-1 as well as SFE/NEP (to a lesser extent) which was followed by distinct increases in their protein and enzymatic activity levels. The addition of AX at concentrations of 4-8 microM immediately after UVA exposure significantly attenuated the induction of MMP-1 and SFE/NEP expression elicited by UVA at the gene, protein and activity levels although both the UVA stimulation and the subsequent AX inhibition were greater for MMP-1 than for SFE/NEP. Analysis of the UVA-induced release of cytokines revealed that UVA significantly stimulated only the secretion of IL-6 among the cytokines tested and that AX significantly diminished only the IL-6 secretion.
  
  
  CONCLUSIONS
  These findings indicate that, based on different effective concentrations of AX, a major mode of action leading to the inhibition elicited by AX depends on inhibition of UVA effects of the reactive oxygen species-directed signaling cascade, but not on interruption of the IL-6-mediated signaling cascade. We hypothesize that AX would have a significant benefit on protecting against UVA-induced skin photo-aging such as sagging and wrinkles.
authors.affiliation: Department of Dermatology, Jichi Medical University, 3311-1 Yakushiji, Shimotuke, Tochigi 329-0498, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Suganuma
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nakajima
authors.forename: Mamitaro
authors.initials: M
authors.lastname: Ohtsuki
authors.forename: Genji
authors.initials: G
authors.lastname: Imokawa
mesh_terms: D002470:Cell Survival; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D015260:Neprilysin / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology* / Q000378:metabolism; D014466:Ultraviolet Rays; D015854:Up-Regulation; D024341:Xanthophylls / Q000494:pharmacology
chemical_list: D017931:DNA Primers; D024341:Xanthophylls; C005948:astaxanthine; D010196:Pancreatic Elastase; D015260:Neprilysin; D020781:Matrix Metalloproteinase 1