BioMetals

, Volume 26, Issue 2, pp 205–227

Zinc-rich inhibitor of apoptosis proteins (IAPs) as regulatory factors in the epithelium of normal and inflamed airways

  • Eugene Roscioli
  • Rhys Hamon
  • Susan Lester
  • Chiara Murgia
  • Janet Grant
  • Peter Zalewski
Article

DOI: 10.1007/s10534-013-9618-2

Cite this article as:
Roscioli, E., Hamon, R., Lester, S. et al. Biometals (2013) 26: 205. doi:10.1007/s10534-013-9618-2

Abstract

Integrity of the airway epithelium (AE) is important in the context of inhaled allergens and noxious substances, particularly during asthma-related airway inflammation where there is increased vulnerability of the AE to cell death. Apoptosis involves a number of signaling pathways which activate procaspases leading to cleavage of critical substrates. Understanding the factors which regulate AE caspases is important for development of strategies to minimize AE damage and airway inflammation, and therefore to better control asthma. One such factor is the essential dietary metal zinc. Zinc deficiency results in enhanced AE apoptosis, and worsened airway inflammation. This has implications for asthma, where abnormalities in zinc homeostasis have been observed. Zinc is thought to suppress the steps involved in caspase-3 activation. One target of zinc is the family of inhibitor of apoptosis proteins (IAPs) which are endogenous regulators of caspases. More studies are needed to identify the roles of IAPs in regulating apoptosis in normal and inflamed airways and to study their interaction with labile zinc ions. This new information will provide a framework for future clinical studies aimed at monitoring and management of airway zinc levels as well as minimising airway damage and inflammation in asthma.

Keywords

Airway epitheliumApoptosisAsthmaInflammationZinc

Abbreviations

AE

Airway epithelium

AEC

Airway epithelial cell

BALF

Bronchoalveolar lavage fluid

BIR

Baculoviral IAP repeat

Cytochrome c

Cyt c

IAP

Inhibitors of apoptosis

OVA

Ovalbumin

ROS

Reactive oxygen species

RING

Really Interesting New Gene

Smac

Second mitochondria-derived activator of caspase

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Eugene Roscioli
    • 1
  • Rhys Hamon
    • 1
  • Susan Lester
    • 2
  • Chiara Murgia
    • 3
  • Janet Grant
    • 4
  • Peter Zalewski
    • 1
  1. 1.Discipline of Medicine, The Basil Hetzel Institute for Translational Research, The Queen Elizabeth Hospital, University of AdelaideWoodvilleAustralia
  2. 2.Rheumatology Unit, Queen Elizabeth Hospital, The Basil Hetzel Institute for Translational ResearchWoodvilleAustralia
  3. 3.National Research Institute of Food and Nutrition (INRAN)RomeItaly
  4. 4.Discipline of Medicine, Population Research & Outcome Studies, University of AdelaideAdelaideAustralia