Augmented glucose use and pentose cycle activity in hepatic endothelial cells after in vivo endotoxemia

Spolarics, Zoltán; Spitzer, John J.

doi:10.1002/hep.1840170415

Cited by 29 publications

(17 citation statements)

References 32 publications

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“…In endothelial cells, low-dose LPS does not stimulate the release of superoxide anion, consistent with the absence of NADPH oxidase [26]. However, parallel to the increase in GLUT1 and G6PD, LPS also stimulates the gene expression and activity of CuZnSOD and SeGPX [13,29,33].…”

Section: Endotoxemia and The Intracellular Oxidant Balancementioning

confidence: 54%

“…After cellular entry, glucose is phosphorylated by hexokinases and the dominant portion of glucose-6-phosphate (G6P) is metabolized by glycolysis. Approximately 3 and 17% of G6P enters the HMS in resting endothelial and Kupffer cells, respectively [16,26]. Glucose oxidation in the HMS generates NADPH by the actions of glucose-6-phosphate dehydrogenase (G6PD) and 6-phospho-gluconate dehydrogenase (6PGD) and produces pentose phosphates.…”

Section: Dual Role Of Hms In the Cellular Oxidant Balancementioning

confidence: 99%

“…It has been shown that cell-associated ROS is higher in these cells during endotoxemia, presumably as a result of mitochondrial dysfunction or conversion of xanthine dehydrogenase to xanthine oxidase [5,18,24,25]. Endothelial cells, however, release no appreciable ROS to the extracellular space after low-dose LPS in vivo [26]. Hepatic phagocyte activation and recruitment take place in the immediate vicinity of sinusoidal endothelial cells (Fig.…”

Section: Oxidative Stress In the Hepatic Sinusoidmentioning

confidence: 99%

“…Nevertheless, the LPS-induced elevated glucose uptake and glycolysis is accompanied by a potentiated glucose entry into the HMS, which is manifested only upon functional challenges in Kupffer and endothelial cells (Fig. 3) [16,26,67]. Namely, stimulation of NADPH-dependent pathways by phorbolester, zymosan, or t-butyl hydroperoxide results in an approximately fivefold greater increase in glucose flux through the HMS in LPS-exposed cells compared with control cells (Fig.…”

Section: Endotoxemia and The Intracellular Oxidant Balancementioning

confidence: 99%

“…Studies from our laboratory indicate that the alterations in the pentose cycle (hexose monophosphate shunt, HMS) are an important adaptive response to oxidative stress during the innate immune response of hepatic sinusoidal cells [16,26,29].…”

Section: Oxidative Stress In the Hepatic Sinusoidmentioning

confidence: 99%

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Endotoxemia, pentose cycle, and the oxidant/antioxidant balance in the hepatic sinusoid

Spolarics

1998

Journal of Leukocyte Biology

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115

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During the innate immune response, excessive release of reactive oxygen species (ROS) from sequestered phagocytes and activated resident macrophages represents the predominant component of oxidative stress in the liver and other tissues. The consequence of oxidative stress is determined by the status and adaptive changes of antioxidant pathways. In this review, we present evidence that the synchronized response of hepatic sinusoidal endothelial cells, the primary sites of phagocyte attachment, plays an important role in defense against phagocyte-derived ROS. An essential component of the metabolic adaptation of hepatic sinusoidal cells to lipopolysaccharide (LPS)-induced oxidative stress is the stimulated expression of glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of the pentose cycle (hexose monophosphate shunt, HMS). All major ROS-metabolic enzymes, i.e., glutathione peroxidase, glutathione reductase, catalase, superoxide dismutases, NADPH oxidase, and nitric oxide synthase, directly or indirectly depend on NADPH, which is produced in the HMS in these cells. The functional significance of up-regulated HMS within a particular cell type depends on the accompanying adaptive changes in ROS-metabolizing enzymes. In LPS-activated Kupffer cells, the elevated expression of glucose transporter GLUT1 and G6PD mainly serves primed production of superoxide anion, hydrogen peroxide, and nitric oxide. In sinusoidal endothelial cells, the LPS-induced response pattern of glucose-and ROS-metabolizing enzymes results in elevated ROS detoxifying capacity. The described studies also suggest the existence of an intercellular oxidant balance between prooxidant Kupffer cells and antioxidant endothelial cells in the hepatic micro-environment. Maintenance of the intercellular oxidant/antioxidant balance between phagocytes and endothelial cells may represent an important mechanism protecting the hepatic parenchyma against exogenous oxidative stress during the inflammatory response. J. Leukoc. Biol. 63: 534-541; 1998.

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Section: Endotoxemia and The Intracellular Oxidant Balancementioning

confidence: 54%

Section: Dual Role Of Hms In the Cellular Oxidant Balancementioning

confidence: 99%

Section: Oxidative Stress In the Hepatic Sinusoidmentioning

confidence: 99%

Section: Endotoxemia and The Intracellular Oxidant Balancementioning

confidence: 99%

Section: Oxidative Stress In the Hepatic Sinusoidmentioning

confidence: 99%

See 3 more Smart Citations

Endotoxemia, pentose cycle, and the oxidant/antioxidant balance in the hepatic sinusoid

Spolarics

1998

Journal of Leukocyte Biology

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115

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Endotoxin Stimulates Hydrogen Peroxide Detoxifying Activity in Rat Hepatic Endothelial Cells

Spolarics¹,

Stein²,

Garcia³

1996

Hepatology

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During endotoxemia, hepatic endothelial cells can be exThe study aimed to assess the effect of lipopolysacchaposed to oxidative stress, because sinusoidal endothelial cells ride (LPS) in vivo (from Escherichia coli, 2 mg/kg body are the first sites of neutrophil adhesion and are in direct weight intraperitoneally) on the production and elimicontact with activated Kupffer cells. 06 mol/L on endothelial cells after saline and LPS this reduced coenzyme is required for the functions of glutatreatment, respectively. No differences were detected in thione peroxidase (via glutathione) and for the stability of H 2 O 2 -stimulated fluorescence between resting and LPS-catalase.12,13 Therefore, the metabolism of glucose through stimulated Kupffer cells. Administration of varying glu-the HMS is potentially important for either the production cose concentrations in vitro significantly decreased the or the elimination of reactive oxygen species (ROS) in cells 14,15 However, lates the gene expression of GLUT1 glucose transporter, gene expression of Se-dependent glutathione peroxidase and glucose-6-phosphate dehydrogenase (G6PD), superoxide CuZn-dependent superoxide dismutase was elevated in endodismutases, and glutathione peroxidase in hepatic endo-thelial cells only. 15 The LPS-induced responses of these functhelial cells. The present data indicate that the LPS-in-tionally related genes of glucose metabolism and ROS-elimiduced metabolic alterations are accompanied by an nating pathways suggested that activated endothelial cells increased H 2 O 2 -detoxifying capacity in hepatic endothe-may have an increased capacity to metabolize hydrogen perlial cells. This may represent a protective mechanism oxide (H 2 O 2 ). Therefore, in the present study, we aimed to against exogenous oxidative stress caused by activated determine whether endotoxemia alters H 2 O 2 detoxifying achepatic phagocytes during inflammation. Our observa-tivity in freshly isolated hepatic endothelial and Kupffer tions are consistent with primed production of reactive cells. We investigated H 2 O 2 metabolism 22 hours after a sinoxygen species (ROS) in LPS-activated Kupffer cells. gle LPS injection intraperitoneally, because this treatment (HEPATOLOGY 1996;24:691-696.)caused alterations in the gene expression of glucose metabolic enzymes and ROS-eliminating pathways in a cell-specific fashion. 15 We also tested the effect of glucose availability and the potential involvement of nitric oxide on H 2 O 2 metabolism Abbreviations: HMS, hexose monophosphate shunt; NADPH, reduced nicotinamide adein these cells.nine dinucleotide phosphate; ROS, reactive oxygen species; LPS, lipopolysaccharide; DCFdiacetate, 2,7-dicholorfluorescin diacetate; L-NMMA, N G -monomethyl-L-arginine; PMA,

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Upregulation of glucose‐6‐phosphate dehydrogenase in response to hepatocellular oxidative stress: Studies with diquat

Cramer

Cooke

Ginsberg

et al. 1995

J. Biochem. Toxicol.

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The expression of hepatic glucose-6-phosphate dehydrogenase (G6PDH, E.C. 1.1.1.49) is hypothesized to be modulated by free radicals during oxidative stress. The ability of diquat, a compound known to enhance oxidative stress through generation of reactive oxygen species, to modulate the expression of G6PDH in primary cultures of Fischer-rat hepatocytes was examined. Diquat-treated hepatocytes maintained in a chemically defined medium showed both a time- and concentration-dependent increase in G6PDH enzyme activity. This increase in enzyme activity was accounted for by an increase in both G6PDH mRNA and immunoreactive protein, suggesting control at a pretranslational level. The possibility that diquat increased transcription by transfecting cells with a chimeric gene containing 935 bp of the G6PDH promoter (-878 to +57) linked to the gene for chloramphenicol acetyl-transferase (CAT) was examined. Hepatocytes transiently transfected with this chimera, and subsequently treated with diquat, exhibited an increase in CAT activity. However, hepatocytes transfected with a chimera containing 287 bp of the G6PDH promoter (-230 to +57) exhibited only basal CAT activity in the presence of diquat. These results suggest that regions in the DNA sequences required for diquat-induced expression of G6PDH lie between base pairs -878 and -230 of the G6PDH gene. These findings are suggestive that oxidative stress in hepatocytes increased the expression of G6PDH activity and protein and that the increased expression is controlled at the transcriptional level.

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Augmented glucose use and pentose cycle activity in hepatic endothelial cells after in vivo endotoxemia

Cited by 29 publications

References 32 publications

Endotoxemia, pentose cycle, and the oxidant/antioxidant balance in the hepatic sinusoid

Endotoxemia, pentose cycle, and the oxidant/antioxidant balance in the hepatic sinusoid

Endotoxin Stimulates Hydrogen Peroxide Detoxifying Activity in Rat Hepatic Endothelial Cells

Upregulation of glucose‐6‐phosphate dehydrogenase in response to hepatocellular oxidative stress: Studies with diquat

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