title: Zinc-rich inhibitor of apoptosis proteins (IAPs) as regulatory factors in the epithelium of normal and inflamed airways.
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.
authors: Discipline of Medicine, The Basil Hetzel Institute for Translational Research, The Queen Elizabeth Hospital, University of Adelaide, Woodville, SA, 5011, Australia. eugene.roscioli@adelaide.edu.au
authors: Eugene
authors: E
authors: Roscioli
authors: Rhys
authors: R
authors: Hamon
authors: Susan
authors: S
authors: Lester
authors: Chiara
authors: C
authors: Murgia
authors: Janet
authors: J
authors: Grant
authors: Peter
authors: P
authors: Zalewski
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001249:Asthma / Q000378:metabolism* / Q000473:pathology; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D061945:Caspase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D020169:Caspases; D015032:Zinc