Endotoxin stimulates gene expression of ROS-eliminating pathways in rat hepatic endothelial and Kupffer cells

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Reactive oxygen species (ROS) are mediators of cellular injury and play a putative role in the onset of hepatic damage during endotoxemia or sepsis. It has been suggested that induction of glucose-6-phosphate (G-6-P) dehydrogenase, the key enzyme of the hexose monophosphate shunt (HMS), may support ROS-producing or ROS-eliminating pathways in hepatic endothelial and Kupffer cells during endotoxemia. The aim of the study was to assess in vivo lipopolysaccharide (LPS)-induced alterations in rat gene expression of selected enzymes that are in functional relationship with the HMS. mRNA levels and activities of glucose transporter GLUT-1, Mn- and CuZn-dependent superoxide dismutases (Mn-SOD and CuZn-SOD), and Se-dependent glutathione peroxidase (Se-GPX) were determined. Cellular extracts were analyzed 7 or 22 h after injection of LPS (Escherichia coli, 2 mg/kg ip) or injection of saline. Exposure to LPS for 7 or 22 h caused a 10- to 25-fold increase in GLUT-1 mRNA levels in endothelial and Kupffer cells. In parenchymal cells, GLUT-1 mRNA expression was low, and LPS caused no marked changes. Cellular levels of Mn-SOD mRNA were 20-40 times greater in all hepatic cells from LPS- treated animals than in cells from control rats. LPS at 22 h increased Mn- SOD activity by 45% in endothelial cells but caused no significant changes in Kupffer or parenchymal cells. Message levels and enzyme activities of CuZn- SOD and Se-GPX were significantly elevated 22 h after LPS injection in endothelial cells only. Thus LPS results in marked upregulation of functionally related genes in hepatic cells. In endothelial cells, the simultaneous upregulation of GLUT-1, G-6-P dehydrogenase, Mn-SOD, CuZn-SOD, and Se-GPX may represent an important mechanism for accelerated elimination of ROS released from activated sinusoidal phagocytes. In Kupffer cells, upregulated GLUT-1 and G-6-P dehydrogenase, together with constitutively present SOD and lack of upregulated Se-GPX, suggest an elevated capacity to produce O2 and H2O2 that is consistent with primed bacterial killing.

Original languageEnglish (US)
Pages (from-to)G660-G666
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number4 33-4
StatePublished - 1996

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


  • GLUT- 1
  • glucose
  • glutathione peroxidase
  • hepatocytes
  • hexose monophosphate shunt
  • hydrogen peroxide
  • lipopolysaccharide
  • liver
  • superoxide anion
  • superoxide dismutase

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