Lipoic acid suppression of neutrophil respiratory burst: effect of NADPH
Lipoic acid (LA) and its reduced product dihydrolipoic acid (DHLA) are potent antioxidants with capacity to scavenge reactive oxygen species (ROS) and recycle endogenous antioxidants. LA may increase cellular glutathione (GSH), an antioxidant lacking in the lung's epithelial lining fluid in lun...
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Published in | Antioxidants & redox signaling Vol. 10; no. 2; p. 277 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
United States
01.02.2008
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Abstract | Lipoic acid (LA) and its reduced product dihydrolipoic acid (DHLA) are potent antioxidants with capacity to scavenge reactive oxygen species (ROS) and recycle endogenous antioxidants. LA may increase cellular glutathione (GSH), an antioxidant lacking in the lung's epithelial lining fluid in lung disorders such as idiopathic pulmonary fibrosis (IPF). Neutrophils (PMN) are key innate responders and are pivotal in clearing bacterial infection, therefore it is crucial to understand the impact LA may have on their function. Circulating neutrophils were isolated from healthy volunteers and pretreated with LA or diluent. Cells were subsequently activated with phorbol 12-myristate 13-acetate (PMA, 100 ng/ml) to induce ROS production. SOD-inhibitable reduction of acetylated cytochrome c demonstrated the PMA-dependent respiratory burst was suppressed by LA. Oxygen consumption also was diminished when PMA-stimulated cells were pretreated with LA. PMN respiratory burst was partially restored by addition of NADPH but not other pyridine nucleotides. LA did not inhibit glucose-6-phosphate dehydrogenase activity of PMN. These data together suggest that the reduction of LA to DHLA using cellular NADPH may limit the capacity of the PMN NADPH oxidase to produce superoxide. Further studies will be required to determine if LA can diminish excessive superoxide produced by PMN and/or alveolar macrophages in IPF or relevant disease models in vivo. |
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AbstractList | Lipoic acid (LA) and its reduced product dihydrolipoic acid (DHLA) are potent antioxidants with capacity to scavenge reactive oxygen species (ROS) and recycle endogenous antioxidants. LA may increase cellular glutathione (GSH), an antioxidant lacking in the lung's epithelial lining fluid in lung disorders such as idiopathic pulmonary fibrosis (IPF). Neutrophils (PMN) are key innate responders and are pivotal in clearing bacterial infection, therefore it is crucial to understand the impact LA may have on their function. Circulating neutrophils were isolated from healthy volunteers and pretreated with LA or diluent. Cells were subsequently activated with phorbol 12-myristate 13-acetate (PMA, 100 ng/ml) to induce ROS production. SOD-inhibitable reduction of acetylated cytochrome c demonstrated the PMA-dependent respiratory burst was suppressed by LA. Oxygen consumption also was diminished when PMA-stimulated cells were pretreated with LA. PMN respiratory burst was partially restored by addition of NADPH but not other pyridine nucleotides. LA did not inhibit glucose-6-phosphate dehydrogenase activity of PMN. These data together suggest that the reduction of LA to DHLA using cellular NADPH may limit the capacity of the PMN NADPH oxidase to produce superoxide. Further studies will be required to determine if LA can diminish excessive superoxide produced by PMN and/or alveolar macrophages in IPF or relevant disease models in vivo. |
Author | Rancourt, Raymond C O'Neill, Heidi C White, Carl W |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/18158760$$D View this record in MEDLINE/PubMed |
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CitedBy_id | crossref_primary_10_1016_j_chom_2017_09_004 crossref_primary_10_1089_ars_2020_8098 crossref_primary_10_1128_JB_00446_19 crossref_primary_10_1155_2022_7450514 crossref_primary_10_3164_jcbn_11_67 crossref_primary_10_3390_molecules23081857 crossref_primary_10_1016_j_intimp_2023_109713 crossref_primary_10_1089_ars_2007_1912 crossref_primary_10_2147_JIR_S358799 crossref_primary_10_1080_10715762_2018_1525712 |
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Snippet | Lipoic acid (LA) and its reduced product dihydrolipoic acid (DHLA) are potent antioxidants with capacity to scavenge reactive oxygen species (ROS) and recycle... |
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SubjectTerms | Bacterial Infections - prevention & control Folic Acid - pharmacology Glucosephosphate Dehydrogenase - blood Humans Kinetics NADP - pharmacology Neutrophils - drug effects Neutrophils - microbiology Neutrophils - physiology Oxygen Consumption Peroxidase - blood Reactive Oxygen Species - metabolism Respiratory Burst - drug effects Respiratory Burst - physiology Superoxides - blood Thioctic Acid - pharmacology |
Title | Lipoic acid suppression of neutrophil respiratory burst: effect of NADPH |
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