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Acute phase proteins are major clients for the chaperone action of α2-macroglobulin in human plasma

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Cell Stress and Chaperones Aims and scope

An Erratum to this article was published on 05 July 2013

Abstract

Extracellular protein misfolding is implicated in many age-related diseases including Alzheimer's disease, macular degeneration and arthritis. In this study, putative endogenous clients for the chaperone activity of α2-macroglobulin (α2M) were identified after human plasma was subjected to physiologically relevant sheer stress at 37 °C for 10 days. Western blot analysis showed that four major acute phase proteins: ceruloplasmin, fibrinogen, α1-acid glycoprotein and complement component 3, preferentially co-purified with α2M after plasma was stressed. Furthermore, the formation of complexes between α2M and these putative chaperone clients, detected by sandwich ELISA, was shown to be enhanced in response to stress. These results support the hypothesis that α2M plays an important role in extracellular proteostasis by sequestering misfolded proteins and targeting them for disposal, particularly during acute phase reactions.

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Acknowledgements

AR Wyatt is grateful for a CJ Martin Fellowship from the National Health and Medical Research Council (NHMRC), Australia and a Junior Research Fellowship, Wolfson College, Cambridge UK. MR Wilson acknowledges financial support for this work from the Centre for Medical Bioscience (University of Wollongong). Blood plasma used in this study was kindly donated by healthy consenting volunteers under the approval of the University of Wollongong and Illawarra Shoalhaven Local Health District Health Medical Human Ethics Committee (HE02/080).

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  1. Department of Chemistry, University of Cambridge, Cambridge, UK

    Amy R. Wyatt

  2. Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia

    Amy R. Wyatt & Mark R. Wilson

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Correspondence to Mark R. Wilson.

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Wyatt, A.R., Wilson, M.R. Acute phase proteins are major clients for the chaperone action of α2-macroglobulin in human plasma. Cell Stress and Chaperones 18, 161–170 (2013). https://doi.org/10.1007/s12192-012-0365-z

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