Oxidation of thiols and modification of redox-sensitive signaling in human lung epithelial cells exposed to Pseudomonas pyocyanin.
The aim of this study was to examine the effects of pyocyanin exposure on mitochondrial GSH, other cellular thiols (thioredoxin-1, Trx-1), and oxidant-sensitive signaling pathways hypoxia inducible factor (HIF-1α) and heme oxygenase (HO-1) in A549 and HBE cell lines. A549 human type II alveolar epithelial cells and human bronchial epithelial (HBE) cells were treated with varying concentrations of pyocyanin extracted from Pseudomonas aeruginosa bacteria. Cytoplasmic and mitochondrial thiols and oxidant sensitive signal transduction proteins (HIF-1α and HO-1) were measured. Exposure to pyocyanin generated reactive oxygen species (ROS) in cellular mitochondria and altered total cellular glutathione (GSH). Pyocyanin, at concentrations present in conditions in vivo, increased oxidized Trx-1 in A549 human type II alveolar epithelial cells and HBE cells by 184 and 74%, respectively. Oxidized mitochondrial glutathione (GSSG) was elevated more than twofold in both cell types. Pyocyanin also increased the cellular oxidant-sensitive proteins HIF-1α and HO-1. Data indicate that pyocyanin-induced alterations in mitochondrial and cytosolic thiols, as well as oxidant-sensitive proteins, may contribute to P. aeruginosa-mediated lung injury.
Department of Radiography, The Hashemite University, Zarqa, Jordan.
Iman M
IM
Ahmad
Bradley E
BE
Britigan
Maher Y
MY
Abdalla
D002460:Cell Line; D004790:Enzyme Induction / Q000187:drug effects; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000187:drug effects / Q000378:metabolism; D015151:Immunoblotting; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects*; D011552:Pseudomonas Infections / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D011710:Pyocyanine / Q000009:adverse effects / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D015398:Signal Transduction / Q000187:drug effects*; D013879:Thioredoxins / Q000187:drug effects / Q000378:metabolism
D051793:Hypoxia-Inducible Factor 1; D017382:Reactive Oxygen Species; C491203:TXN protein, human; D013879:Thioredoxins; D011710:Pyocyanine; D006419:Heme Oxygenase (Decyclizing); D005978:Glutathione