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

Other Title
일차 배양 혈관 평활근 세포에서 포도당 농도에 의한 엔도톡신 유도 프로스타글란딘 합성 변화
Authors
이, 수환; 우, 현구; 김, 지영; 백, 은주; 문, 창현
Citation
Yakhakhoe chi, 41(6):782-788, 1997
Journal Title
Yakhakhoe chi; Journal of the Pharmaceutical Society of Korea; 약학회지
ISSN
0377-9556
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 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 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 and PGHS which resulted in the augmentation in LPS-induced PG production in high glucose treated VSMC.
Keywords
ProstaglandinEndotoxinVascular smooth muscle cellsHigh glucose
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Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
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