Selenium attenuates lipopolysaccharide-induced oxidative stress responses through modulation of p38 MAPK and NF-kappaB signaling pathways.
Lipopolysaccharide (LPS) produces reactive oxygen species (ROS) and nitric oxide (NO) in macrophages. These molecules are involved in inflammation associated with endotoxic shock. Selenium (Se), a biologically essential trace element, modulates the functions of many regulatory proteins involved in signal transduction and affects a variety of cellular activities, including cell growth and survival. We demonstrate that Se attenuated LPS-induced ROS and NO production in murine macrophage cultures in vitro. This Se-decreased production of NO was demonstrated by decreases in both mRNA and protein expression for inducible NO synthase (iNOS). The preventive effects of Se on iNOS were p38 mitogen-activated protein kinase- and nuclear factor-kappaB-dependent. Se specifically blocked the LPS-induced activation of p38 but not that of c-jun-N-terminal kinase and extracellular signal-regulated kinase; the p38-specific pathway was confirmed using p38 inhibitor SB 203580. These results suggest that the mechanism by which Se may act as an anti-inflammatory agent and that Se may be considered as a possible preventive intervention for endotoxemia, particularly in Se-deficient locations. However, the efficacy and safety of Se need to be further investigated, because long-term intake > 0.4 mg Se/day in adults can produce adverse effects.
Kim
Sang Hyun
SH
Department of Physiology and Pharmacology, College of Veterinary Medicine, The University of Georgia, Athens, 30602, USA.
Johnson
Victor J
VJ
Shin
Tae-Yong
TY
Sharma
Raghubir P
RP
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000032:analysis / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism; D012643:Selenium / Q000494:pharmacology*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases
D004791:Enzyme Inhibitors; D007093:Imidazoles; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011725:Pyridines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D004247:DNA; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione; D012643:Selenium; C093642:SB 203580