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 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.
Ricciarelli
R
R
Institut für Biochemie und Molekularbiologie, Universität Bern, Switzerland.
Maroni
P
P
Ozer
N
N
Zingg
J M
JM
Azzi
A
A
D000328:Adult; D000367:Age Factors; D000368:Aged; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005347:Fibroblasts; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D007527:Isoenzymes / Q000378:metabolism*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D012333:RNA, Messenger / Q000378:metabolism; D015595:Skin Aging / Q000187:drug effects; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014810:Vitamin E / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D014810:Vitamin E; D003094:Collagen; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D017364:Collagenases; D020781:Matrix Metalloproteinase 1