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

  • Chao Wang
  • Marion Bouchecareilh
  • William E. Balch
Protocol
Part of the Methods in Molecular Biology book series (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.

Key words

Alpha-1 antitrypsin deficiency Cellular proteostasis Histone deacetylase inhibitor Proteostasis regulators 

Notes

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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Copyright information

© Springer Science+Business Media LLC 2017

Authors and Affiliations

  • Chao Wang
    • 1
  • Marion Bouchecareilh
    • 2
  • William E. Balch
    • 1
  1. 1.Department of Molecular Medicine, The Skaggs Institute for Chemical BiologyThe Scripps Research InstituteLa JollaUSA
  2. 2.Institut de Biochimie et Génétique Cellulaires, CNRS UMR 5095Université de BordeauxBordeauxFrance

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