The formation of intracellular nitrogen-based oxidants has important physiological and pathological consequences. CK (creatine kinase), which plays a key role in intracellular energy metabolism, is a main target of low concentrations of oxidative and nitrative stresses. In the present study, the interaction between cytosolic CKs [MM-CK (muscle-type CK) and BB-CK (brain-type CK)] and MTs [metallothioneins; hMT2A (human MT-IIA) and hMT3 (human MT-III)] were characterized by both in vitro and intact-cell assays. MTs could successfully protect the cytosolic CKs against inactivation induced by low concentrations of PN (peroxynitrite) and NO both in vitro and in hMT2A-overexpressing H9c2 cells and hMT3-knockdown U-87 MG cells. Under high PN concentrations, CK formed granule-like structures, and MTs were well co-localized in these aggregated granules. Further analysis indicated that the number of cells containing the CK aggregates negatively correlated with the expression levels of MTs. In vitro experiments indicated that MTs could effectively protect CKs against aggregation during refolding, suggesting that MT might function as a chaperone to assist CK re-activation. The findings of the present study provide direct evidence of the connection between the two well-characterized intracellular systems: the precisely balanced energy homoeostasis by CKs and the oxidative-stress response system using MTs.
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Research Article|
December 21 2011
Metallothioneins protect cytosolic creatine kinases against stress induced by nitrogen-based oxidants
Zhe Chen;
Zhe Chen
*State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China
†Protein Science Laboratory of the Ministry of Education, School of Life Sciences, Tsinghua University, Beijing 100084, China
‡National Engineering Laboratory for Anti-tumor Protein Therapeutics, School of Life Sciences, Tsinghua University, Beijing 100084, China
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Jie Li;
Jie Li
†Protein Science Laboratory of the Ministry of Education, School of Life Sciences, Tsinghua University, Beijing 100084, China
‡National Engineering Laboratory for Anti-tumor Protein Therapeutics, School of Life Sciences, Tsinghua University, Beijing 100084, China
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Tong-Jin Zhao;
Tong-Jin Zhao
1
*State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China
†Protein Science Laboratory of the Ministry of Education, School of Life Sciences, Tsinghua University, Beijing 100084, China
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Xu-Hui Li;
Xu-Hui Li
*State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China
†Protein Science Laboratory of the Ministry of Education, School of Life Sciences, Tsinghua University, Beijing 100084, China
‡National Engineering Laboratory for Anti-tumor Protein Therapeutics, School of Life Sciences, Tsinghua University, Beijing 100084, China
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Fan-Guo Meng;
Fan-Guo Meng
§Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, Zhejiang, China
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Hang Mu;
Hang Mu
†Protein Science Laboratory of the Ministry of Education, School of Life Sciences, Tsinghua University, Beijing 100084, China
§Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, Zhejiang, China
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Yong-Bin Yan;
Yong-Bin Yan
2
*State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China
2Correspondence may be addressed to either of these authors (email ybyan@tsinghua.edu.cn or zhm-dbs@tsinghua.edu.cn).
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Hai-Meng Zhou
Hai-Meng Zhou
2
†Protein Science Laboratory of the Ministry of Education, School of Life Sciences, Tsinghua University, Beijing 100084, China
‡National Engineering Laboratory for Anti-tumor Protein Therapeutics, School of Life Sciences, Tsinghua University, Beijing 100084, China
§Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, Zhejiang, China
2Correspondence may be addressed to either of these authors (email ybyan@tsinghua.edu.cn or zhm-dbs@tsinghua.edu.cn).
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Publisher: Portland Press Ltd
Received:
August 29 2011
Revision Received:
October 02 2011
Accepted:
October 03 2011
Accepted Manuscript online:
October 03 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem J (2012) 441 (2): 623–632.
Article history
Received:
August 29 2011
Revision Received:
October 02 2011
Accepted:
October 03 2011
Accepted Manuscript online:
October 03 2011
Citation
Zhe Chen, Jie Li, Tong-Jin Zhao, Xu-Hui Li, Fan-Guo Meng, Hang Mu, Yong-Bin Yan, Hai-Meng Zhou; Metallothioneins protect cytosolic creatine kinases against stress induced by nitrogen-based oxidants. Biochem J 15 January 2012; 441 (2): 623–632. doi: https://doi.org/10.1042/BJ20111565
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