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Lab Invest. 2015 Feb;95(2):142-56. doi: 10.1038/labinvest.2014.147. Epub 2015 Jan 12.

Endogeous sulfur dioxide protects against oleic acid-induced acute lung injury in association with inhibition of oxidative stress in rats.

Author information

1
Department of Pediatrics, Peking University First Hospital, Beijing, China.
2
Department of Emergency, Beijing Jishuitan Hospital, Beijing, China.
3
1] Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China [2] Department of Gasotransmitters and Cardiovascular Diseases, Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing, China.
4
1] Department of Pediatrics, Peking University First Hospital, Beijing, China [2] Department of Gasotransmitters and Cardiovascular Diseases, Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing, China.

Abstract

The role of endogenous sulfur dioxide (SO2), an efficient gasotransmitter maintaining homeostasis, in the development of acute lung injury (ALI) remains unidentified. We aimed to investigate the role of endogenous SO2 in the pathogenesis of ALI. An oleic acid (OA)-induced ALI rat model was established. Endogenous SO2 levels, lung injury, oxidative stress markers and apoptosis were examined. OA-induced ALI rats showed a markedly downregulated endogenous SO2/aspartate aminotransferase 1 (AAT1)/AAT2 pathway and severe lung injury. Chemical colorimetry assays demonstrated upregulated reactive oxygen species generation and downregulated antioxidant capacity in OA-induced ALI rats. However, SO2 increased endogenous SO2 levels, protected against oxidative stress and alleviated ALI. Moreover, compared with OA-treated cells, in human alveolar epithelial cells SO2 downregulated O2(-) and OH(-) generation. In contrast, L-aspartic acid-β-hydroxamate (HDX, Sigma-Aldrich Corporation), an inhibitor of endogenous SO2 generating enzyme, promoted free radical generation, upregulated poly (ADP-ribose) polymerase expression, activated caspase-3, as well as promoted cell apoptosis. Importantly, apoptosis could be inhibited by the free radical scavengers glutathione (GSH) and N-acetyl-L-cysteine (NAC). The results suggest that SO2/AAT1/AAT2 pathway might protect against the development of OA-induced ALI by inhibiting oxidative stress.

PMID:
25581610
DOI:
10.1038/labinvest.2014.147
[Indexed for MEDLINE]
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