Oxidative stress resistance through blocking Hsp60 translocation followed by SAPK/JNK inhibition in aged human diploid fibroblasts |
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Authors: | Young‐Hee Lee Bhattarai Govinda Jae‐Cheol Kim Tae‐Il Kim Nan‐Hee Lee Jung‐Chang Lee Ho‐Keun Yi Eun‐Chung Jhee |
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Institution: | 1. Department of Oral Biochemistry, School of Dentistry, Chonbuk National University, Korea;2. Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Korea;3. Department of Sports Science, College of Nature Science, Chonbuk National University, Korea;4. Hanwoo Experiment Station, National Institute of Animal Science, RDA, Pyongchang, Korea |
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Abstract: | 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. Copyright © 2008 John Wiley & Sons, Ltd. |
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Keywords: | SAPK/JNK SP600125 SAPK/JNK inhibitor heat shock protein60 human diploid fibroblasts oxidative stress |
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