Melittin-induced hyperactivation of phospholipase A2 activity and calcium influx in ras-transformed cells.
Melittin-induced hyperactivation of phospholipase A2 activity and calcium influx in ras-transformed cells.
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作者：
Sreenath V. Sharma
激活的ras癌基因是细胞转化的关键介质，存在于多种原发性人类肿瘤中。ras癌基因在细胞转化中的生物化学作用目前尚不清楚，因此控制其在转化细胞中的活性的方法取得了有限的成功。先前的研究已经证明蜂毒肽（蜂毒肽，一种来自蜂毒的26个氨基酸的两亲性肽）能够特异性地反选择培养物中表达高水平ras癌基因产物的细胞。这种反选择的生物化学基础目前尚不清楚。这项研究表明蜂毒肽的能力，超激活磷脂酶A2（PLA2）在ras转化细胞的介导的钙离子（Ca2+）的增加流入。这种超活化的PLA2和Ca2+动员ras转化细胞蜂毒肽是模仿的钙离子载体，A23187。蜂毒肽和A23187介导的PLA2超活化都需要Ca~（2+）。然而，蜂毒肽的作用强烈依赖于细胞外Ca~（2+），而A23187则不依赖。蜂毒肽诱导的Ca~（2+）内流和PLA_2超活化可被锰离子（Mn~（2+））抑制。这些研究揭示了PLA2超活化程度和Ca2+动员之间的密切相关性，表明存在因果关系。
The activated ras oncogene is a key mediator of cellular transformation and is present in a wide variety of primary human neoplasms. The biochemical role of the ras oncogene in cellular transformation is at present unclear, and hence approaches to control its activities in transformed cells have met with limited success. Previous studies have demonstrated the ability of melittin, a 26 amino acid amphipathic peptide from bee venom, to specifically counterselect for cells in culture that express high levels of the ras oncogene product. The biochemical basis for this counterselection is currently unknown. This study demonstrates the ability of melittin to hyperactivate phospholipase A2 (PLA2) in ras-transformed cells by the mediation of enhanced influx of calcium ions (Ca2+). This hyperactivation of PLA2 and Ca2+ mobilization in ras-transformed cells by melittin is mimicked by the calcium ionophore, A23187. Both melittin- and A23187-mediated PLA2 hyperactivation require Ca2+. However, the action of melittin is strongly dependent on extracellular Ca2+, whereas that of A23187 is not. Melittin-induced Ca2+ influx and PLA2 hyperactivation is inhibited by manganese ions (Mn2+). These studies reveal a close correlation between the extent of PLA2 hyperactivation and Ca2+ mobilization, suggesting a causal relationship.