Metabolism of arachidonic acid in human lung cancer cell lines.
Metabolism of arachidonic acid in human lung cancer cell lines.
复制标题
花生四烯酸在人肺癌细胞系中的代谢。
作者：
Serrine S. Lau;Serrine S. Lau;James B. McMahon;M. McMenamin;Hildegard M. Schuller;Michael R. Boyd
研究了两种肺细支气管肺泡癌细胞系（NCI-H322 和 NCI-H358）和两种小细胞肺癌细胞系（NCI-H69 和 NCI-H128）中花生四烯酸（AA）的代谢。外源AA仅在NCI-H322和NCI-H358细胞中代谢。无论是否存在钙离子载体 A23187，NCI-H69 或 NCI-H128 细胞中均未检测到 AA 代谢。从 NCI-H322 和 NCI-H358 细胞中分离出的 AA 的主要代谢物是前列腺素 E2 (PGE2)。 NCI-H358 和 NCI-H322 细胞中前列腺素内过氧化物合酶活性（以免疫反应性 PGE2（pmol/min/mg 蛋白）表示）分别为 10.3 +/- 0.28 (SD) 和 4.8 +/- 0.48。 NCI-H358 和 NCI-H322 细胞产生 PGE2 的速率在 10 分钟内呈线性。两种细胞系中 PGE2 的产生均取决于底物浓度，并且在 17 microM AA 以上时达到最大。此外，PGE2 没有经过NCI-H358 或NCI-H322 细胞的进一步代谢。阿司匹林 (0.1 mM) 是一种环氧合酶抑制剂，可使 NCI-H358 和 NCI-H322 细胞中 PGE2 的产生分别减少 77% 和 60%。在外源 AA 存在的情况下，钙离子载体 A23187 (20 µM) 将 NCI-H322 细胞中 PGE2 的产生刺激近 2 倍，但它并不影响 NCI-H358 细胞中 PGE2 的产生。相比之下，A23187 在 NCI-H322 和 NCI-H358 细胞中分别刺激 PGE2 的内源性产生 4 倍和 9 倍。此外，NCI-H358和NCI-H322细胞系都以时间和浓度依赖性方式对抗癌剂米托蒽醌的细胞毒性作用敏感。相比之下，缺乏可检测的前列腺素合成活性的两种细胞系NCI-H69和NCI-H128未受到米托蒽醌处理的影响。这些结果说明人类肺癌细胞系生物合成和释放PGE2的能力存在重大差异。可以想象，这种差异可能具有可利用的诊断和/或治疗意义。
The metabolism of arachidonic acid (AA) was studied in two pulmonary bronchioloalveolar-carcinoma cell lines (NCI-H322 and NCI-H358) and two small cell lung carcinoma cell lines (NCI-H69 and NCI-H128). Exogenous AA was metabolized only in the NCI-H322 and NCI-H358 cells. There was no detectable metabolism of AA in NCI-H69 or NCI-H128 cells, either in the presence or the absence of the calcium ionophore A23187. The major metabolite of AA isolated from both NCI-H322 and NCI-H358 cells was prostaglandin E2 (PGE2). Prostaglandin endoperoxide synthase activities, expressed as immunoreactive PGE2 (pmol/min/mg protein), were 10.3 +/- 0.28 (SD) and 4.8 +/- 0.48 in NCI-H358 and NCI-H322 cells, respectively. The rate of production of PGE2 by both NCI-H358 and NCI-H322 cells was linear up to 10 min. Production of PGE2 in both cell lines was dependent upon substrate concentration and was maximal above 17 microM AA. Moreover, PGE2 did not undergo further metabolism by either the NCI-H358 or the NCI-H322 cells. Aspirin (0.1 mM), a cyclooxygenase inhibitor, decreased PGE2 production by 77 and 60% in NCI-H358 and NCI-H322 cells, respectively. In the presence of exogenous AA the calcium ionophore, A23187 (20 microM), stimulated PGE2 production in NCI-H322 cells by almost 2-fold, although it did not affect PGE2 production in the NCI-H358 cells. In contrast, A23187 stimulated the endogenous production of PGE2 in both NCI-H322 and NCI-H358 cells by 4- and 9-fold respectively. In addition, both the NCI-H358 and NCI-H322 cell lines were susceptible to the cytotoxic effects of the anticancer agent mitoxantrone in both a time and concentration dependent manner. In contrast, the two cell lines lacking detectable prostaglandin synthesis activity, NCI-H69 and NCI-H128 were unaffected by treatment with mitoxantrone. These results illustrate that there are major differences in the abilities of human lung cancer cell lines to biosynthesize and release PGE2. It is conceivable that such differences might have exploitable diagnostic and/or therapeutic implications.
药物和外源性物质的肾脏代谢。
影响因子：
2.5
作者：
Davis,BB;Mattammal,MB;Zenser,TV
通讯作者：
Zenser,TV