IL-1 (interleukin-1) acts as a key mediator of the degeneration of articular cartilage in RA (rheumatoid arthritis) and OA (osteoarthritis), where chondrocyte death is observed. It is still controversial, however, whether IL-1 induces chondrocyte death. In the present study, the viability of mouse chondrocyte-like ATDC5 cells was reduced by the treatment with IL-1β for 48 h or longer. IL-1β augmented the expression of the catalytic gp91 subunit of NADPH oxidase, gp91phox, as well as inducible NO synthase in ATDC5 cells. Generation of nitrated guanosine and tyrosine suggested the formation of reactive nitrogen species including ONOO− (peroxynitrite), a reaction product of NO and O2−, in ATDC5 cells and rat primary chondrocytes treated with IL-1β. Death of ATDC5 cells after IL-1β treatment was prevented by an NADPH-oxidase inhibitor, AEBSF [4-(2-aminoethyl)benzenesulphonyl fluoride], an NO synthase inhibitor, L-NAME (NG-nitro-L-arginine methyl ester), and a ONOO− scavenger, uric acid. The viability of ATDC5 cells was reduced by the ONOO−-generator 3-(4-morpholinyl)sydnonimine hydrochloride, but not by either the NO-donor 1-hydroxy-2-oxo-3-(N-methyl-2-aminopropyl)-3-methyl-1-triazene or S-nitrosoglutathione. Disruption of mitochondrial membrane potential and ATP deprivation were observed in IL-1β-treated ATDC5 cells, both of which were restored by L-NAME, AEBSF or uric acid. On the other hand, no morphological or biochemical signs indicating apoptosis were observed in these cells. These results suggest that the death of chondrocyte-like ATDC5 cells was mediated at least in part by mitochondrial dysfunction and energy depletion through ONOO− formation after IL-1β treatment.
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Research Article|
July 05 2005
Interleukin-1β induces death in chondrocyte-like ATDC5 cells through mitochondrial dysfunction and energy depletion in a reactive nitrogen and oxygen species-dependent manner
Rika Yasuhara;
Rika Yasuhara
*Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555, Japan
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Yoichi Miyamoto;
Yoichi Miyamoto
1
*Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555, Japan
1To whom correspondence should be addressed (email yoichim@dent.showa-u.ac.jp).
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Takaaki Akaike;
Takaaki Akaike
†Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
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Teruo Akuta;
Teruo Akuta
†Department of Microbiology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan
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Masanori Nakamura;
Masanori Nakamura
‡Department of Oral Anatomy and Developmental Biology, Showa University School of Dentistry, Tokyo 142-8555, Japan
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Masamichi Takami;
Masamichi Takami
*Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555, Japan
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Naoko Morimura;
Naoko Morimura
*Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555, Japan
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Kayoko Yasu;
Kayoko Yasu
*Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555, Japan
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Ryutaro Kamijo
Ryutaro Kamijo
*Department of Biochemistry, Showa University School of Dentistry, Tokyo 142-8555, Japan
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Publisher: Portland Press Ltd
Received:
December 01 2004
Revision Received:
March 17 2005
Accepted:
March 23 2005
Accepted Manuscript online:
March 23 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 389 (2): 315–323.
Article history
Received:
December 01 2004
Revision Received:
March 17 2005
Accepted:
March 23 2005
Accepted Manuscript online:
March 23 2005
Citation
Rika Yasuhara, Yoichi Miyamoto, Takaaki Akaike, Teruo Akuta, Masanori Nakamura, Masamichi Takami, Naoko Morimura, Kayoko Yasu, Ryutaro Kamijo; Interleukin-1β induces death in chondrocyte-like ATDC5 cells through mitochondrial dysfunction and energy depletion in a reactive nitrogen and oxygen species-dependent manner. Biochem J 15 July 2005; 389 (2): 315–323. doi: https://doi.org/10.1042/BJ20041996
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