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

Total protein kinase C (PKC) activity in human skin fibroblasts increases d uring 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 inc rease in total PKC activity is mainly due to the PKC alpha isoform. PKC alp ha protein expression increased up to 8 fold during in vivo aging. Collagen ase (MMP-1) gene transcription and protein expression also increased with a ge, concomitant with the increase in protein kinase C alpha. Furthermore, a lpha-tocopherol, which inhibits protein kinase C activity, is able to dimin ish collagenase gene transcription without altering the level of its natura l 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 in creased collagen degradation. Our in vitro experiments with skin fibroblast s suggest that alpha-tocopherol may protect against skin aging by decreasin g the level of collagenase expression, which is induced by environmental in sults and by aging. (C) 1999 Elsevier Science Inc.