Expression of cysteine dioxygenase (EC 1.13.11.20) and sulfite oxidase in the human lung: a potential role for sulfate production in the protection from airborne xenobiotica.
OBJECTIVE
The lung is one of the major sites of phase I cytochrome P450 enzyme and phase II sulfotransferase expression, which together are thought to act as an enzymic barrier against the unimpeded transfer of airborne xenobiotics into the lung parenchyma and systemic circulation. Sulfate for conjugation is produced primarily from the oxidation of cysteine, begun by cysteine dioxygenase (CDO), and completed with the conversion of sulfite to sulfate via sulfite oxidase (SO). Little is known about the site of expression of these two enzymes in the alveoli of the human lung.


METHODS
Antibodies and oligonucleotide probes raised against both CDO and SO were used for immunohistochemistry and in situ hybridisation, respectively, to investigate the expression of CDO and SO in human lung alveoli.


RESULTS
CDO and SO were expressed in alveolar epithelial cells, which is also the site of expression of cytochrome P450 1B1.


CONCLUSIONS
These results demonstrate that the two key enzymes in sulfate production are expressed in the same locale as phase I and phase II enzymes, and that these two enzymes may be involved in the production of sulfate for the maintenance of a metabolic barrier against the entry of airborne xenobiotics and the synthesis of important structural proteins and proteoglycans.
D000393:Air Pollutants / Q000493:pharmacokinetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D050558:Cysteine Dioxygenase; D065633:Cytochrome P-450 CYP1B1; D049308:Dioxygenases; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008658:Inactivation, Metabolic / Q000502:physiology; D008297:Male; D008875:Middle Aged; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000201:enzymology* / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism; D015262:Xenobiotics / Q000493:pharmacokinetics*
D000393:Air Pollutants; D013431:Sulfates; D015262:Xenobiotics; D010105:Oxygenases; D049308:Dioxygenases; D050558:Cysteine Dioxygenase; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D050862:Oxidoreductases Acting on Sulfur Group Donors