Age-dependent increase of collagenase expression can be reduced by alpha-tocopherol via protein kinase C inhibition

Free Radic Biol Med. 1999 Oct;27(7-8):729-37. doi: 10.1016/s0891-5849(99)00007-6.


Total protein kinase C (PKC) activity in human skin fibroblasts increases during in vivo aging as a function of the donor's age. During in vitro aging protein kinase C activity is also increased, as a function of cell passage number. Using PKC isoform specific antibodies, we demonstrate that the increase in total PKC activity is mainly due to the PKC a isoform. PKC alpha protein expression increased up to 8 fold during in vivo aging. Collagenase (MMP-1) gene transcription and protein expression also increased with age, concomitant with the increase in protein kinase C alpha. Furthermore, alpha-tocopherol, which inhibits protein kinase C activity, is able to diminish collagenase gene transcription without altering the level of its natural inhibitor, tissue inhibitor of metalloproteinase, TIMP-1. We propose that an aging program leads to increased protein kinase C alpha expression and activity. This event would induce collagenase overexpression followed by increased collagen degradation. Our in vitro experiments with skin fibroblasts suggest that alpha-tocopherol may protect against skin aging by decreasing the level of collagenase expression, which is induced by environmental insults and by aging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Cells, Cultured
  • Collagen / metabolism
  • Collagenases / genetics
  • Collagenases / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Female
  • Fibroblasts
  • Gene Expression Regulation, Enzymologic / drug effects
  • Humans
  • Infant, Newborn
  • Isoenzymes / metabolism*
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism*
  • Middle Aged
  • Protein Kinase C / metabolism*
  • Protein Kinase C-alpha
  • RNA, Messenger / metabolism
  • Skin Aging / drug effects
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Transcription, Genetic / drug effects
  • Vitamin E / pharmacology*


  • Enzyme Inhibitors
  • Isoenzymes
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1
  • Vitamin E
  • Collagen
  • PRKCA protein, human
  • Protein Kinase C
  • Protein Kinase C-alpha
  • Collagenases
  • Matrix Metalloproteinase 1