title: Impairment of lon-induced protection against the accumulation of oxidized proteins in senescent wi-38 fibroblasts.
abstract: Oxidative damage to mitochondrial proteins is thought to contribute to the aging process, but the Lon protease normally degrades such proteins. In early-passage WI-38 human lung fibroblasts, Lon expression is rapidly induced during H(2)O(2) stress, which prevents the accumulation of oxidized proteins and protects cell viability. In contrast, middle passage cells exhibit only sluggish induction of Lon expression in oxidative stress, and oxidized proteins initially accumulate. Late-passage, or senescent, cells have low basal levels of Lon and high levels of accumulated oxidized proteins; in response to oxidative stress, they fail to induce Lon expression and exhibit continually increasing accumulation of oxidized proteins. Senescent cells separated into two populations, one exhibiting normal mitochondrial mass and a second displaying significant loss of mitochondria; both populations had diminished mitochondrial transmembrane potential. These senescent changes are similar to the effects of Lon silencing in young cells. We suggest that loss of Lon stress inducibility is part of a pattern of diminishing stress adaptability that predisposes cells to senescence.
authors.affiliation: Ethel Percy Andrus Gerontology Center, University of Southern California, Los Angeles, CA 90089-0191, USA.
authors.forename: Jenny K
authors.initials: JK
authors.lastname: Ngo
authors.forename: Laura C D
authors.initials: LC
authors.lastname: Pomatto
authors.forename: Daniela A
authors.initials: DA
authors.lastname: Bota
authors.forename: Alison L
authors.initials: AL
authors.lastname: Koop
authors.forename: Kelvin J A
authors.initials: KJ
authors.lastname: Davies
mesh_terms: D000222:Adaptation, Physiological; D015153:Blotting, Western; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D024101:Mitochondrial Proteins / Q000378:metabolism / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D049070:Protease La / Q000502:physiology*; D059748:Proteolysis; D014407:Tumor Cells, Cultured
chemical_list: D024101:Mitochondrial Proteins; D049070:Protease La