Differential effect of oxidative stress on the apoptosis of early and late passage human diploid fibroblasts: implication of heat shock protein 60.
Since an attenuated response to stress is a characteristic of senescence, a cellular senescence model was used to examine the mechanism of resistance against oxidative stress using human diploid fibroblasts (HDF). With increasing passage, the HDF showed increased production of reactive oxygen species (ROS). Late passage HDF were resistant to the lethal effects of oxidative stress, showing less cleavage of pro-caspase-3 and PARP than those of early ones. Since heat shock proteins (Hsps) are not only cytoprotective but also interfere with the apoptotic cascade, the expression patterns of Hsps during cellular senescence were next examined. Oxidative stress induced a decrease in the mitochondrial Hsp60 levels with a concomitant increase in the cytosolic Hsp60 levels in the early passage HDF, but not in late ones. To show that the resistance to oxidative stress is a specific effect of Hsp60, the levels of Hsp60 were knocked down by siRNA. As expected the Hsp60 knock-down cells were more resistant to oxidative stress. These findings show that Hsp60 is a key player in the resistance mechanism against oxidative stress and aging.
Lee
Young-Hee
YH
Department of Oral Biochemistry, School of Dentistry, Chonbuk National University, Korea.
Lee
Jung-Chang
JC
Moon
Hyun-Ju
HJ
Jung
Ji-Eun
JE
Sharma
Manju
M
Park
Byung-Hyun
BH
Yi
Ho-Keun
HK
Jhee
Eun-Chung
EC
D017209:Apoptosis / Q000187:drug effects; D048430:Cell Shape; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism*; D004171:Diploidy; D005347:Fibroblasts; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
D018834:Chaperonin 60; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide