Duodenal cytochrome b: a novel ferrireductase in airway epithelial cells.
Catalytically active iron in the lung causes oxidative stress and promotes microbial growth that can be limited by intracellular sequestration of iron within ferritin. Because cellular iron uptake requires membrane ferrireductase activity that in the gut can be provided by duodenal cytochrome b (Dcytb), we sought Dcytb in the lung to test the hypothesis that it contributes to epithelial iron regulation by reducing Fe(3+) for cellular iron transport. Dcytb expression was found in respiratory epithelium in vitro and in vivo and was responsive to iron concentration. Iron transport was measured in human bronchial epithelial (HBE) cells using inductively coupled plasma atomic emission spectroscopy and was demonstrated to be partially inhibited in the presence of Dcytb-blocking antibody, suggesting that Dcytb reduces Fe(3+) for cellular iron transport. A definite source of reducing equivalents for Dcytb was sought but not identified. We found no evidence that ascorbate was involved but did demonstrate that O(2)(-). production decreased when Dcytb function was blocked. The presence of Dcytb in airway epithelial cells and its regulation by iron therefore may contribute to pulmonary cytoprotection.
Turi
Jennifer L
JL
Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA. turi0002@mc.duke.edu
Wang
Xinchao
X
McKie
Andrew T
AT
Nozik-Grayck
Eva
E
Mamo
Lisa B
LB
Crissman
Kay
K
Piantadosi
Claude A
CA
Ghio
Andrew J
AJ
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D002478:Cells, Cultured; D045303:Cytochromes b / Q000235:genetics / Q000378:metabolism*; D004386:Duodenum / Q000166:cytology / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000166:cytology* / Q000378:metabolism
D016166:Free Radical Scavengers; D045303:Cytochromes b; D007501:Iron; D001205:Ascorbic Acid