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Text
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URL Address
<a href="http://doi.org/10.1016/j.freeradbiomed.2018.01.013" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.freeradbiomed.2018.01.013</a>
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Pages
159-171
Volume
116
Dublin Core
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Title
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Nrf2/ARE pathway attenuates oxidative and apoptotic response in human osteoarthritis chondrocytes by activating ERK1/2/ELK1-P70S6K-P90RSK signaling axis.
Publisher
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Free radical biology & medicine
Date
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2018
2018-02
Subject
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Humans; *Apoptosis; *Apoptosis; *ERK1/2; *Nrf2; *Osteoarthritis; *Redox; Oxidative Stress; Osteoarthritis/*metabolism; NF-E2-Related Factor 2/genetics/*metabolism; Up-Regulation; MAP Kinase Signaling System; Chondrocytes/*physiology; Caspases/metabolism; Cells; Cultured; 70-kDa/metabolism; Ribosomal Protein S6 Kinases; Carboxylic Ester Hydrolases/metabolism; ets-Domain Protein Elk-1/metabolism; Interleukin-1beta/immunology; 90-kDa/metabolism
Creator
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Khan Nazir M; Ahmad Imran; Haqqi Tariq M
Description
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Nrf2, a redox regulated transcription factor, has recently been shown to play a role in cartilage integrity but the mechanism remains largely unknown. Osteoarthritis (OA) is a multifactorial disease in which focal degradation of cartilage occurs. Here, we studied whether Nrf2 exerts chondroprotective effects by suppressing the oxidative stress and apoptosis in IL-1beta stimulated human OA chondrocytes. Expression of Nrf2 and its target genes HO-1, NQO1 and SOD2 was significantly high in OA cartilage compared to normal cartilage and was also higher in damaged area compared to smooth area of OA cartilage of the same patient. Human chondrocytes treated with IL-1beta resulted in robust Nrf2/ARE reporter activity, which was inhibited by pretreatment with antioxidants indicating that Nrf2 activity was due to IL-1beta-induced ROS generation. Ectopic expression of Nrf2 significantly suppressed the IL-1beta-induced generation of ROS while Nrf2 knockdown significantly increased the basal as well as
Identifier
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<a href="http://doi.org/10.1016/j.freeradbiomed.2018.01.013" target="_blank" rel="noreferrer noopener">10.1016/j.freeradbiomed.2018.01.013</a>
*Apoptosis
*ERK1/2
*Nrf2
*OSTEOARTHRITIS
*Redox
2018
70-kDa/metabolism
90-kDa/metabolism
Ahmad Imran
Carboxylic Ester Hydrolases/metabolism
Caspases/metabolism
Cells
Chondrocytes/*physiology
Cultured
ets-Domain Protein Elk-1/metabolism
Free radical biology & medicine
Haqqi Tariq M
Humans
Interleukin-1beta/immunology
Khan Nazir M
MAP Kinase Signaling System
NF-E2-Related Factor 2/genetics/*metabolism
Osteoarthritis/*metabolism
Oxidative Stress
Ribosomal Protein S6 Kinases
Up-Regulation