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Measuring the Effect of Histone Deacetylase Inhibitors (HDACi) on the Secretion and Activity of Alpha-1 Antitrypsin

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Alpha-1 Antitrypsin Deficiency

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1639))

Abstract

Alpha-1 antitrypsin deficiency (AATD) is a protein conformational disease with the most common cause being the Z-variant mutation in alpha-1 antitrypsin (Z-AAT). The misfolded conformation triggered by the Z-variant disrupts cellular proteostasis (protein folding) systems and fails to meet the endoplasmic reticulum (ER) export metrics, leading to decreased circulating AAT and deficient antiprotease activity in the plasma and lung. Here, we describe the methods for measuring the secretion and neutrophil elastase (NE) inhibition activity of AAT/Z-AAT, as well as the response to histone deacetylase inhibitor (HDACi), a major proteostasis modifier that impacts the secretion and function of AATD from the liver to plasma. These methods provide a platform for further therapeutic development of proteostasis regulators for AATD.

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Acknowledgments

This work was supported by grants from National Institute of Health HL095524 for WEB. CW is supported by a postdoctoral research fellowship from Alpha-1 Foundation.

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Authors and Affiliations

  1. Department of Molecular Medicine, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA

    Chao Wang & William E. Balch

  2. Institut de Biochimie et Génétique Cellulaires, CNRS UMR 5095, Université de Bordeaux, Bordeaux, France

    Marion Bouchecareilh

Authors
  1. Chao Wang
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  2. Marion Bouchecareilh
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  3. William E. Balch
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Corresponding author

Correspondence to William E. Balch .

Editor information

Editors and Affiliations

  1. Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Florie Borel

  2. Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Christian Mueller

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Wang, C., Bouchecareilh, M., Balch, W.E. (2017). Measuring the Effect of Histone Deacetylase Inhibitors (HDACi) on the Secretion and Activity of Alpha-1 Antitrypsin. In: Borel, F., Mueller, C. (eds) Alpha-1 Antitrypsin Deficiency . Methods in Molecular Biology, vol 1639. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7163-3_18

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  • DOI: https://doi.org/10.1007/978-1-4939-7163-3_18

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7161-9

  • Online ISBN: 978-1-4939-7163-3

  • eBook Packages: Springer Protocols

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