Sakayama K, Masuno H, Okumura H, Shibata T, Okuda H
Department of Orthopaedic Surgery, School of Medicine, Ehime University, Japan.
Biochem J. 1996 Jun 15;316 ( Pt 3)(Pt 3):813-7. doi: 10.1042/bj3160813.
The effect of recombinant human tumour necrosis factor-alpha (TNF-alpha) on synthesis, activity and secretion of lipoprotein lipase (LPL) was examined using a human osteosarcoma cell line, osteosarcoma Takase (OST). Treatment of OST cells with TNF-alpha decreased LPL synthesis, resulting in a decrease in expression of activity and secretion of LPL. When OST cells were incubated with glycerol tri[1-14C]palmitate, TNF-alpha decreased dose- and time-dependently the production of 14CO2 and the amounts of radioactivity incorporated into cellular triacylglycerol and phospholipid. The similar reduction of synthesis and activity of LPL as suppression of CO2 production and cellular lipid synthesis indicated that the suppression of 14CO2 production and 14C-labelled lipid synthesis was secondary. TNF-alpha also suppressed expression of proliferating cell nuclear antigen, indicating that it had an anti-proliferative activity on OST cells. The findings suggest that one cause of the anti-proliferative activity of TNF-alpha is the suppression of the LPL-mediated supply of non-esterified fatty acids as an energy source for growth.
使用人骨肉瘤细胞系骨肉瘤高濑(OST)研究了重组人肿瘤坏死因子-α(TNF-α)对脂蛋白脂肪酶(LPL)合成、活性和分泌的影响。用TNF-α处理OST细胞可降低LPL合成,导致LPL活性表达和分泌减少。当OST细胞与三[1-14C]棕榈酸甘油酯一起孵育时,TNF-α剂量和时间依赖性地降低了14CO2的产生以及掺入细胞三酰甘油和磷脂中的放射性量。LPL合成和活性的类似降低与CO2产生和细胞脂质合成的抑制表明,14CO2产生和14C标记的脂质合成的抑制是次要的。TNF-α还抑制增殖细胞核抗原的表达,表明它对OST细胞具有抗增殖活性。这些发现表明,TNF-α抗增殖活性的一个原因是抑制LPL介导的非酯化脂肪酸供应作为生长的能量来源。