Oxidative stress resistance through blocking Hsp60 translocation followed by SAPK/JNK inhibition in aged human diploid fibroblasts.
The stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) pathway is a well-known senescence-related stress activated protein kinase. Multiple environmental stresses induce programmed cell death, such as apoptosis. Normal human diploid fibroblast (HDF) cells have a limited life span in vitro, halting proliferation after a fixed number of cell divisions. Aged passage HDF showed resistance to oxidative stress involving heat shock proteins (Hsp60) through a mechanism involving the translocation of Hsp60 from the mitochondria to the cytosol. The present study showed that the translocation of Hsp60 from the mitochondria to the cytosol followed by high levels of p-SAPK/JNK activation as a result of oxidative stress was observed in the young cells only. The inhibition of SAPK/JNK activation by SP600125 under oxidative stress almost completely blocked the translocation of Hsp60 in both young and aged cells. This suggests that aged HDF cells are resistant to oxidative stress by blocking the translocation of Hsp60 from the mitochondria to the cytosol followed by SAPK/JNK inhibition. Overall, the mechanism of resistance by oxidative stress in aged cells is induced by blocked of the translocation of Hsp60 followed by SAPK/JNK inactivation.
Lee
Young-Hee
YH
Department of Oral Biochemistry, School of Dentistry, Chonbuk National University, Korea.
Govinda
Bhattarai
B
Kim
Jae-Cheol
JC
Kim
Tae-Il
TI
Lee
Nan-Hee
NH
Lee
Jung-Chang
JC
Yi
Ho-Keun
HK
Jhee
Eun-Chung
EC
D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D018834:Chaperonin 60 / Q000378:metabolism*; D004171:Diploidy; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology
D000873:Anthracenes; D018834:Chaperonin 60; D024101:Mitochondrial Proteins; C432165:pyrazolanthrone; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases