The Korean Journal of Physiology and Pharmacology
- 제3권4호
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- Pages.447-454
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- 1999
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- 1226-4512(pISSN)
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- 2093-3827(eISSN)
The Enhancement of Endotoxin-Induced Nitric Oxide Production by Elevation of Glucose Concentration in Macrophage
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Woo, Hyun-Goo
(Department of Physiology, School of Medicine, Ajou University) ;
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Jung, Yi-Sook
(Department of Physiology, School of Medicine, Ajou University) ;
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Baik, Eun-Joo
(Department of Physiology, School of Medicine, Ajou University) ;
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Moon, Chang-Hyun
(Department of Physiology, School of Medicine, Ajou University) ;
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Lee, Soo-Hwan
(Department of Physiology, School of Medicine, Ajou University)
- 발행 : 1999.08.21
초록
The production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) are known to be modulated by a variety of factors. Recent study showed that endotoxin-induced NO synthesis and iNOS expression were greatly enhanced by elevation of extracellular glucose concentration in murine macrophages. Although this was suggested to be due to the activation of protein kinase C (PKC) via sorbitol pathway, there was lack of evidence for this speculation. This study was performed to delineate the underlying intracellular mechanisms of glucose-enhancing effect on endotoxin-induced NO production in Raw264.7 macrophages. The levels of NO release induced by lipopolysaccharide (LPS) significantly increased by the treatment of glucose in a concentration dependent manner and also, this effect was observed in LPS-preprimed cells. Concurrent incubation of cells with PKC inhibitors, H-7 or chelerythrine, and LPS resulted in the diminution of NO production regardless of glucose concentration but this was not in the case of LPS-prepriming, that is, chelerythrine showed a minimal effect on the glucose- enhancing effect. PMA, a PKC activator, did not show any significant effect on glucose-associated NO production. Modulation of sorbitol pathway with zopolrestat, an aldose reductase inhibitor, did not affect LPS-induced NO production and iNOS expression under high glucose condition. And also, sodium pyruvate, which is expected to normalize cytosolic