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Glutathione S-transferase omega in the lung and sputum supernatants of COPD patients
Authors:Terttu H Harju  Mirva J Peltoniemi  Paula H Rytilä  Ylermi Soini  Kaisa M Salmenkivi  Philip G Board  Lloyd W Ruddock  Vuokko L Kinnula
Institution:1. Department of Internal Medicine, University of Oulu, Oulu, Finland
2. Biocenter Oulu and Department of Biochemistry, University of Oulu, Oulu, Finland
3. Department of Medicine, Division of Allergology, University of Helsinki, Helsinki, Finland
6. Department of Pathology, Oulu University Hospital, Oulu, Finland
8. Department of Clinical Pathology and Forensic Medicine, University of Kuopio, Kuopio, Finland
4. Department of Pathology, Helsinki University Hospital, Helsinki, Finland
5. John Curtin School of Medical Research, Australian National University, Canberra, Australia
7. Department of Medicine, Division of Pulmonary Diseases, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Abstract:

Background

The major contribution to oxidant related lung damage in COPD is from the oxidant/antioxidant imbalance and possibly impaired antioxidant defence. Glutathione (GSH) is one of the most important antioxidants in human lung and lung secretions, but the mechanisms participating in its homeostasis are partly unclear. Glutathione-S-transferase omega (GSTO) is a recently characterized cysteine containing enzyme with the capability to bind and release GSH in vitro. GSTO has not been investigated in human lung or lung diseases.

Methods

GSTO1-1 was investigated by immunohistochemistry and Western blot analysis in 72 lung tissue specimens and 40 sputum specimens from non-smokers, smokers and COPD, in bronchoalveolar lavage fluid and in plasma from healthy non-smokers and smokers. It was also examined in human monocytes and bronchial epithelial cells and their culture mediums in vitro.

Results

GSTO1-1 was mainly expressed in alveolar macrophages, but it was also found in airway and alveolar epithelium and in extracellular fluids including sputum supernatants, bronchoalveolar lavage fluid, plasma and cell culture mediums. The levels of GSTO1-1 were significantly lower in the sputum supernatants (p = 0.023) and lung homogenates (p = 0.003) of COPD patients than in non-smokers.

Conclusion

GSTO1-1 is abundant in the alveolar macrophages, but it is also present in extracellular fluids and in airway secretions, the levels being decreased in COPD. The clinical significance of GSTO1-1 and its role in regulating GSH homeostasis in airway secretions, however, needs further investigations.
Keywords:
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