title: Alpha-tocopherol modulates hydrogen peroxide-induced DNA damage and telomere shortening of human skin fibroblasts derived from differently aged individuals.
abstract: Antioxidants such as vitamin E may act differently on skin cells depending on the age of the skin and the level of oxidative damage induced. The effects of alpha-tocopherol (ATF) on H(2)O(2)-induced DNA damage and telomere shortening of normal human skin fibroblast cells derived from young and old individual donors were determined. Fibroblasts were divided into five groups; untreated control, H(2)O(2)-induced oxidative stress, alpha-tocopherol treatment, and pre- and post-treatment with alpha-tocopherol for H(2)O(2)-induced oxidative stress. Our results showed that H(2)O(2)-induced oxidative stress increased DNA damage, shortened the telomere length and reduced the telomerase activity (p < 0.05) in fibroblasts obtained from young and old donors. Pre- and post-treatment with alpha-tocopherol protected against H(2)O(2)-induced DNA damage in fibroblasts obtained from young individuals (p = 0.005; p = 0.01, respectively). However, in fibroblasts obtained from old individuals, similar protective effects were only seen in cells pretreated with alpha-tocopherol (p = 0.05) but not in the post-treated cells. Protection against H(2)O(2)-induced telomere shortening was observed in fibroblasts obtained from both young and old donors which were pre-treated with alpha-tocopherol (p = 0.009; p = 0.008, respectively). However, similar protective effects against telomere shortening in fibroblasts obtained from both young and old donors were not observed in the post-treated fibroblasts. Protection against H(2)O(2)-induced telomerase activity loss was observed only in fibroblasts obtained from old donors which were pretreated with alpha-tocopherol (p = 0.04) but not in fibroblasts obtained from young donors. Similar protective effects against telomerase activity loss in fibroblasts obtained from both young and old donors were not observed in the post-treated fibroblasts. In conclusion, alpha-tocopherol protected against H(2)O(2)-induced telomere shortening by restoring the telomerase activity. It also modulated H(2)O(2)-induced DNA damage and this modulation was affected by donor age.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, National University of Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, Malaysia. suzanamakpol@yahoo.com
authors.forename: Suzana
authors.initials: S
authors.lastname: Makpol
authors.forename: Azalina
authors.initials: A
authors.lastname: Zainuddin
authors.forename: Norhazira Abdul
authors.initials: NA
authors.lastname: Rahim
authors.forename: Yasmin Anum
authors.initials: YA
authors.lastname: Yusof
authors.forename: Wan Zurinah
authors.initials: WZ
authors.lastname: Ngah
mesh_terms: D000367:Age Factors; D016922:Cellular Senescence / Q000187:drug effects* / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects*; D004334:Drug Administration Schedule; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide; D018384:Oxidative Stress / Q000187:drug effects*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000187:drug effects* / Q000648:ultrastructure; D024502:alpha-Tocopherol / Q000494:pharmacology*
chemical_list: D006861:Hydrogen Peroxide; D019098:Telomerase; D024502:alpha-Tocopherol