Earl C Q, Stadel J M, Anzano M A
Department of Clinical Investigation, Smith Kline and French Laboratories, King of Prussia, Pennsylvania 19406-0939.
J Biol Response Mod. 1990 Aug;9(4):361-7.
The guanine nucleotide binding protein (G-protein) dependency of several of the activities of tumor necrosis factor (TNF), including cytotoxicity, inhibition of lipoprotein lipase activity, blockade of 3T3-L1 differentiation, and receptor binding were examined. TNF induced killing of the TNF-sensitive cell line L929S (ED50 = 30 pM), but had little to no effect on the TNF-resistant cell line L929R (ED50 = 5,300 pM). TNF-induced cytotoxicity in L929S was antagonized in a dose-dependent manner by pertussis toxin (sevenfold increase in ED50). However, TNF-induced cytotoxicity in L929R cells was only minimally affected by pretreatment with a high dose (50 ng/ml) of pertussis toxin (1.5-fold increase in ED50). Parallel biochemical investigations revealed that inhibition was accompanied by toxin-induced ADP ribosylation of a Gi alpha-like subunit in L929 and 3T3-L1 cell membranes. Pertussis toxin also significantly reduced TNF-induced inhibition of lipoprotein lipase activity in 3T3-L1 adipocytes and TNF blockade of 3T3-L1 preadipocyte differentiation. However, pertussis toxin pretreatment of L929S, L929R, and 3T3-L1 cell cultures had little to no effect on TNF receptor binding. These data indicate that several TNF-induced biological activities in the L929 and 3T3-L1 cell lines are partially dependent upon a pertussis toxin-sensitive G-protein.
对肿瘤坏死因子（TNF）的几种活性（包括细胞毒性、脂蛋白脂肪酶活性抑制、3T3-L1分化阻断和受体结合）的鸟嘌呤核苷酸结合蛋白（G蛋白）依赖性进行了研究。TNF可诱导TNF敏感细胞系L929S的杀伤（ED50 = 30 pM），但对TNF耐药细胞系L929R几乎没有影响（ED50 = 5300 pM）。百日咳毒素以剂量依赖的方式拮抗L929S中TNF诱导的细胞毒性（ED50增加7倍）。然而，高剂量（50 ng/ml）百日咳毒素预处理对L929R细胞中TNF诱导的细胞毒性影响极小（ED50增加1.5倍）。平行的生化研究表明，抑制作用伴随着毒素诱导的L929和3T3-L1细胞膜中一种类似Giα亚基的ADP核糖基化。百日咳毒素还显著降低了TNF诱导的3T3-L1脂肪细胞中脂蛋白脂肪酶活性的抑制以及TNF对3T3-L1前脂肪细胞分化的阻断。然而，百日咳毒素预处理L929S、L929R和3T3-L1细胞培养物对TNF受体结合几乎没有影响。这些数据表明，L929和3T3-L1细胞系中几种TNF诱导的生物学活性部分依赖于对百日咳毒素敏感的G蛋白。
