Sugar-induced premature aging and altered differentiation in human epidermal keratinocytes.
Normal human epidermal keratinocytes (NHEK) show both the Hayflick phenomenon and differentiation in vitro. The aim of this study was to induce senescence in keratinocytes using two sugars, glucose and glyoxal. Induction of senescence in early-passage NHEK was characterized by monitoring cell morphology, short-term growth characteristics, cell proliferation, and viability assay. In addition, apoptosis, senescence-associated (SA) beta-gal activity, proteasomal activity and glycation, and glycoxidation of total proteins were determined. Our results show that a 3-day treatment with 100 mM glucose or 0.1 mM glyoxal induces in early-passage NHEK various cellular and biochemical characteristics comparable to those observed in serially subcultured late passage NHEK. Furthermore, sugar-treated prematurely aged NHEK showed impaired differentiation, as measured by the quantification of involucrin. There is preliminary evidence that a preexposure of NHEK to mild heat shock (41 degrees C, 1 h, 6 h in advance) can abrogate some of the sugar-induced negative effects, which is an example of mild stress-induced hormesis. This experimental model can be useful to study the effects of potential antiaging interventions.
Berge
Ulrich
U
Department of Molecular Biology, University of Aarhus, Gustav Wieds Vej 10C, DK8000 Aarhus-C, Denmark.
Behrens
Juliane
J
Rattan
Suresh I S
SI
D002241:Carbohydrates / Q000494:pharmacology*; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000078404:Epidermal Cells; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006037:Glyoxal / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology*; D012867:Skin / Q000166:cytology; D013997:Time Factors
D002241:Carbohydrates; D006360:Heat-Shock Proteins; D006037:Glyoxal; D005947:Glucose