Apoptosis in the normal and inflamed airway epithelium: role of zinc in epithelial protection and procaspase-3 regulation.
The epithelium lining the airways is a physical barrier as well as a regulator of physiological and pathological events in the respiratory system. Damage to the epithelium by oxidants released from inflammatory cells is a critical factor in the pathogenesis of airway inflammatory diseases such as bronchial asthma. In these diseases, excessive apoptosis may be a likely mechanism responsible for damage to, and sloughing, of airway epithelial cells. Factors that increase the airway epithelium's resilience to apoptosis are likely to lessen the severity of this disease. One such factor is the dietary metal zinc. A special role for labile intracellular pools of zinc as anti-apoptotic agents in the regulation of the caspases, has emerged over the past two decades. This review focuses on caspase-inhibitory functions of zinc in airway epithelial cells, apparent abnormalities of zinc homeostasis in asthmatics and studies from the authors' laboratory which showed that zinc was strategically localized in the apical cytoplasm of airway epithelium to control caspase-3 activated apoptosis. These findings are discussed in the context of recent data from a murine model of allergic asthma, showing that loss of airway epithelial zinc was accompanied by changes in levels of both procaspase-3 and active caspase-3 and that nutritional zinc deprivation further increased airway epithelial apoptosis. We hypothesize that zinc has a protective role for the airway epithelium against oxyradicals and other noxious agents, with important implications for asthma and other inflammatory diseases where the epithelial barrier is vulnerable and compromised.
Truong-Tran
Ai Q
AQ
Department of Medicine, University of Adelaide, The Queen Elizabeth Hospital, Woodville, South Australia 5011, Australia.
Grosser
Dion
D
Ruffin
Richard E
RE
Murgia
Chiara
C
Zalewski
Peter D
PD
D000818:Animals; D017209:Apoptosis; D001249:Asthma / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D004792:Enzyme Precursors / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000187:drug effects / Q000473:pathology; D014105:Tosyl Compounds / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology*
D004792:Enzyme Precursors; D020011:Protective Agents; D015363:Quinolones; D014105:Tosyl Compounds; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D015032:Zinc; C084731:zinquin