title: Cultured murine dermal fibroblast-like cells from senescence-accelerated mice as in vitro models for higher oxidative stress due to mitochondrial alterations.
abstract: The senescence-accelerated mouse is a model for senescence acceleration, a higher oxidative stress status, and age-associated disorders. We studied whether fibroblasts cultured from accelerated senescence-prone SAMP11 mice could be used as in vitro models for oxidative stress in senescence. Dichlorofluorescein and hydroethidine assays demonstrated that cells from SAMP11 mice produced more reactive oxygen species than did cells from accelerated senescence-resistant SAMR1 mice. These differences were not due to the defective induction of antioxidants. Double labeling with hydroethidine and MitoTracker Green revealed that most of the reactive oxygen species were generated within the mitochondria. Nonyl acridine orange and JC-1 assays showed an increase in the mass of the mitochondria, especially those with low membrane potential, in SAMP11 cells. Ultrastructurally, mitochondria with degenerative morphology were increased in SAMP11 cells with longer culture periods. These results suggest that cells from SAMP11 mice are useful models for spontaneous higher oxidative stress in vitro due to dysfunctional mitochondria.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Kyoto University, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Chiba
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Masaki
authors.initials: M
authors.lastname: Ueno
authors.forename: Hiromi
authors.initials: H
authors.lastname: Fujisawa
authors.forename: Kazunori
authors.initials: K
authors.lastname: Hirayoshi
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Hohmura
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Tomimoto
authors.forename: Ichiro
authors.initials: I
authors.lastname: Akiguchi
authors.forename: Mamoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Atsuyoshi
authors.initials: A
authors.lastname: Shimada
authors.forename: Masanori
authors.initials: M
authors.lastname: Hosokawa
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000648:ultrastructure; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000166:cytology*
chemical_list: D012333:RNA, Messenger; D017382:Reactive Oxygen Species