Cultured murine dermal fibroblast-like cells from senescence-accelerated mice as in vitro models for higher oxidative stress due to mitochondrial alterations.
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.
Chiba
Yoichi
Y
Department of Neurology, Graduate School of Medicine, Kyoto University, Japan.
Yamashita
Yoshinori
Y
Ueno
Masaki
M
Fujisawa
Hiromi
H
Hirayoshi
Kazunori
K
Hohmura
Ken-Ichi
K
Tomimoto
Hidekazu
H
Akiguchi
Ichiro
I
Satoh
Mamoru
M
Shimada
Atsuyoshi
A
Hosokawa
Masanori
M
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*
D012333:RNA, Messenger; D017382:Reactive Oxygen Species