Simulated microgravity promotes cellular senescence via oxidant stress in rat PC12 cells.
Microgravity has a unique effect on biological organisms. Organs exposed to microgravity display cellular senescence, a change that resembles the aging process. To directly investigate the influence of simulated microgravity on neuronal original rat PC12 cells, we used a rotary cell culture system that simulates the microgravity environment on the earth. We found that simulated microgravity induced partial G1 phase arrest, upregulated senescence-associated beta-galactosidase (SA-beta-gal) activity, and activated both p53 and p16 protein pathways linked to cell senescence. The amount of reactive oxygen species (ROS) was also increased. The activity of intracellular antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT), was all significantly increased at 12h after the microgravity onset, yet decreased at 96h. Furthermore, concomitant block of ROS by the antioxidant N-acetylcysteine significantly inhibited the microgravity-induced upregulation of SA-beta-gal activity. These results suggest that exposure to simulated microgravity induces cellular senescence in PC12 cells via an increased oxidant stress.
Wang
Jinghua
J
Department of Neurobiology, Harbin Medical University, Heilongjiang, China.
Zhang
Jifei
J
Bai
Shasha
S
Wang
Guangyou
G
Mu
Lili
L
Sun
Bo
B
Wang
Dandan
D
Kong
Qingfei
Q
Liu
Yumei
Y
Yao
Xiuhua
X
Xu
Ying
Y
Li
Hulun
H
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D016922:Cellular Senescence / Q000502:physiology*; D005434:Flow Cytometry; D016166:Free Radical Scavengers / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D009474:Neurons / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014893:Weightlessness / Q000009:adverse effects*; D001616:beta-Galactosidase / Q000378:metabolism
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D001616:beta-Galactosidase; D000111:Acetylcysteine