YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Enhancement of Endotoxin-Induced Prostaglandin Synthesis by Elevation of Glucose Concentration in Primary Cultured Rat Vascular Smooth Muscle Cells

일차 배양 혈관 평활근 세포에서 포도당 농도에 의한 엔도톡신 유도 프로스타글란딘 합성 변화

  • Lee, Soo-Hwan (Department of Physiology, School of Medicine, Ajou University) ;
  • Woo, Hyun-Goo (Department of Physiology, School of Medicine, Ajou University) ;
  • Kim, Ji-Young (Department of Physiology, School of Medicine, Ajou University) ;
  • Baik, Eun-Joo (Department of Physiology, School of Medicine, Ajou University) ;
  • Moon, Chang-Hyun (Department of Physiology, School of Medicine, Ajou University)
  • 이수환 (아주대학교 의과대학 생리학교실) ;
  • 우현구 (아주대학교 의과대학 생리학교실) ;
  • 김지영 (아주대학교 의과대학 생리학교실) ;
  • 백은주 (아주대학교 의과대학 생리학교실) ;
  • 문창현 (아주대학교 의과대학 생리학교실)
  • Published : 1997.12.01
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Abstract

This study was designed to characterize glucose-enhancing effects on endotoxin-induced prostaglandin production in primary cultured rat vascular smooth muscle cells (VSMC). High glucose treatment significantly augmented prostaglandin (PG) synthesis in lipopolysaccharide (LPS)-stimulated VSMC and this effect was maximal at the concentration of 4mg/ml. It has been reported that increases in glucose metabolism through sorbitol pathway could alter the cytosolic $NADH/NAD^+$ ratio and this change favors de novo synthesis of diacylglycerol (DAG) and, in turn. Results in the activation of protein kinase C (PKC) in vascular tissues. Protein kinase C (PKC) inhibitors, staurosporin and H7, blocked the glucose enhancing effect, and DAG, a PKC activator, significantly increased the PG production stimuated by LPS. Sodium pyruvate, which can reverse the alteration in cytosolic NADH/NAD+ ratio, reduced the high glucose effect on PG production. And also, zopolrestat, a strong aldose reductase inhibitor, almost completely blocked the augmentation effect of glucose on PG synthesis. Arachidonic acid release was significantly increased in high glucose treated group, which implied the increase in $PLA_2$ activity was associated with glucose enhancing effect. Metabloic, labeling study clearly showed that de novo synthesis of prostaglandin H synthase-2 (PGHS-2) is greatly increased in high glucose treated group and this was mitigated by the treatment of zopolrestat. Taken together, the activation of PKC through sorbitol pathway increased the activities of $PLA_2$ and PGHS which resulted in the augmentation in LPS-induced PG production in high glucose treated VSMC.

Keywords

References

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