ORIGINAL ARTICLE

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

J Millard¹, R B Parsons², R H Waring¹, A C Williams³, D B Ramsden²

¹ School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
² Department of Medicine, University of Birmingham
³ Neuroscience Centre, Queen Elizabeth Hospital, Birmingham B15 2TH.

Correspondence to:
Correspondence to:
Dr R B Parsons, Neurodegeneration Unit, Department of Medical Sciences (Surgery), St George’s Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK;
r.parsons{at}sghms.ac.uk

Aims: 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.

Keywords: cysteine dioxygenase; cytochrome P450; lung; alveoli; sulfation; sulfite oxidase

Abbreviations: CDO, cysteine dioxygenase; DAB, diaminobenzidine; PAP, peroxidase–antiperoxidase; PAPs, phosphoadenosine-5'-phosphosulfate; SO, sulfite oxidase

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Zhang, X., Vincent, A. S., Halliwell, B., Wong, K. P. (2004). A Mechanism of Sulfite Neurotoxicity: DIRECT INHIBITION OF GLUTAMATE DEHYDROGENASE. J. Biol. Chem. 279: 43035-43045 [Abstract] [Full Text]