title: Endogeous sulfur dioxide protects against oleic acid-induced acute lung injury in association with inhibition of oxidative stress in rats.
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.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Siyao
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Emergency, Beijing Jishuitan Hospital, Beijing, China.
authors.forename: Saijun
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Emergency, Beijing Jishuitan Hospital, Beijing, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Chaoshu
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Emergency, Beijing Jishuitan Hospital, Beijing, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Junbao
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Hongfang
authors.initials: H
authors.lastname: Jin
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D055371:Acute Lung Injury / Q000139:chemically induced* / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001216:Asparagine / Q000031:analogs & derivatives / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000378:metabolism; D015153:Blotting, Western; D003124:Colorimetry; D005453:Fluorescence; D005978:Glutathione / Q000494:pharmacology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019301:Oleic Acid / Q000009:adverse effects*; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013458:Sulfur Dioxide / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D013458:Sulfur Dioxide; C024848:beta-aspartylhydroxamic acid; D019301:Oleic Acid; D001216:Asparagine; D001219:Aspartate Aminotransferases; D005978:Glutathione; D000111:Acetylcysteine