Superoxide dismutase 1 knock-down induces senescence in human fibroblasts.
Reactive oxygen species (ROS) such as superoxide radicals are responsible for the pathogenesis of various human diseases. ROS are generated during normal metabolic process in all of the oxygen-utilizing organisms. The copper-zinc-containing SOD (SOD1) acts as a major defense against ROS by detoxifying the superoxide anion. In model organisms, SOD1 has been shown to play a role in the aging process. However, the exact role of the SOD1 protein in the human aging process remains to be resolved. We show that SOD1 RNA interference (RNAi) induces senescence in normal human fibroblasts. This premature senescence depends on p53 induction. In contrast, in human fibroblastic cells with inactivated p53, the SOD1 RNAi is without effect. Surprisingly, in cancer cells (HeLa), the SOD1 RNAi induces cell death rather then senescence. Together, these findings support the notion that in normal human cells the SOD1 protein may play a role in the regulation of cellular lifespan by p53 and may also regulate the death signals in cancer cells.
Blander
Gil
G
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
de Oliveira
Rita Machado
RM
Conboy
Caitlin M
CM
Haigis
Marcia
M
Guarente
Leonard
L
D000375:Aging; D000838:Anions; D015153:Blotting, Western; D016923:Cell Death; D002460:Cell Line; D016922:Cellular Senescence; D005347:Fibroblasts / Q000378:metabolism*; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D008856:Microscopy, Fluorescence; D010100:Oxygen / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D034622:RNA Interference; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D019076:Transgenes; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
D000838:Anions; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D013482:Superoxide Dismutase; D001616:beta-Galactosidase; D010100:Oxygen