Hori H, Takeuchi S, Matsunaga T, Nakashima S, Nozawa Y
Department of Orthopaedic Surgery, Gifu University, School of Medicine, Japan.
Nihon Seikeigeka Gakkai Zasshi. 1991 Dec;65(12):1191-8.
The cytotoxic mechanism of recombinant human tumor necrosis factor (TNF) in human osteosarcoma cells (TE85) was studied from the point of view of phospholipid metabolism. The TNF-induced cytotoxicity, determined by using the dye uptake method, was dose-dependent in the range of 100-10,000 U/ml. Phospholipid metabolism was analyzed in the cells labelled with [3H] arachidonic acid or [3H] glycerol. TNF stimulated the release of arachidonic acid and its metabolites from the cells in a dose-dependent manner. After TNF stimulation, the level of phosphatidylcholine (PC) decreased. Concomitantly, phospholipase A2 (PLA2) hydrolyzed PC producing a transiently increased level of lysophosphatidylcholine. ONO-RS-082, a potent PLA2 inhibitor, reduced the TNF-induced cytotoxicity and the release of arachidonic acid. These observations suggest that PLA2 may play a role in the cytotoxic effect of TNF on human osteosarcoma cells.
从磷脂代谢的角度研究了重组人肿瘤坏死因子（TNF）对人骨肉瘤细胞（TE85）的细胞毒性机制。采用染料摄取法测定，TNF诱导的细胞毒性在100-10,000 U/ml范围内呈剂量依赖性。用[3H]花生四烯酸或[3H]甘油标记细胞后，分析其磷脂代谢。TNF以剂量依赖的方式刺激细胞释放花生四烯酸及其代谢产物。TNF刺激后，磷脂酰胆碱（PC）水平降低。同时，磷脂酶A2（PLA2）水解PC，使溶血磷脂酰胆碱水平短暂升高。强效PLA2抑制剂ONO-RS-082可降低TNF诱导的细胞毒性和花生四烯酸的释放。这些观察结果表明，PLA2可能在TNF对人骨肉瘤细胞的细胞毒性作用中发挥作用。
