title: Acute glucose overload potentiates nitric oxide production in lipopolysaccharide-stimulated macrophages: the role of purinergic receptor activation.
abstract: The positive effects of high glucose on the cellular productivity of nitric oxide (NO), and the mechanisms of the enhancement, were investigated. Macrophages were shifted from normal-glucose medium (5.5 mM) to high-glucose medium (25 mM) and immediately treated with lipopolysaccharide (LPS). Inducible nitric oxide synthase (iNOS) expression was expressed significantly more quickly, and NO production also increased. High-glucose conditions reduced cell viability at 48 h. Pretreatment with oxidized adenosine triphosphate (o-ATP), the selective purinergic receptor antagonist, strongly reduced LPS-induced iNOS expression, NO production and cell death in cells exposed to high levels of glucose. Apyrase, an ATP-hydrolyzing enzyme, also reduced the effects of high-glucose content. High-glucose content promoted the LPS-induced release of endogenous ATP from RAW 264.7 cells, as measured by luciferin-luciferase assay. In summary, the results revealed that purinergic receptor is important in responding to LPS challenge, increasing LPS-induced NO production and cell death under high-glucose conditions, and promoting the release of ATP from macrophages in high-glucose medium.
authors.affiliation: Department of Medical Technology, Yuanpei University of Science and Technology, Hsinchu, Taiwan. yjchen@mail.yust.edu.tw
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Chen
authors.forename: Kai-Wen
authors.initials: KW
authors.lastname: Hsu
authors.forename: Yun-Liang
authors.initials: YL
authors.lastname: Chen
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005947:Glucose / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010529:Peritoneal Cavity / Q000166:cytology; D011983:Receptors, Purinergic / Q000502:physiology*
chemical_list: D008070:Lipopolysaccharides; D011983:Receptors, Purinergic; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D052247:Nitric Oxide Synthase Type II; D005947:Glucose