Cellular responses to excess phospholipid
Cellular responses to excess phospholipid
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DOI：
10.1074/jbc.274.14.9400
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发表时间：
1999-04-02
影响因子：
4.8
通讯作者：
Jackowski, S
中科院分区：
文献类型：
--
作者：
Baburina, I;Jackowski, S
磷脂酰胆碱（Phosphatidylcholine, PtdCho）是哺乳动物细胞中主要的膜磷脂，其合成受磷脂酰胆碱转移酶（phosphocholine cytidyyl -transferase， CCT）活性的控制，CCT表达增强可加快PtdCho的合成速度。然而，细胞PtdCho的数量并没有因为PtdCho的胆碱和甘油成分的转换而增加。代谢标记实验表明，细胞通过将PtdCho降解为甘油酰胆碱（GPC）来补偿CCT活性升高。磷脂酶d介导的PtdCho水解和磷脂胆碱的形成不受影响，由于过量磷脂的产生而产生的大部分GPC被分泌到培养基中。当暴露于外源性溶血磷脂酰胆碱或溶血磷脂乙醇胺增加磷脂形成时，细胞也将多余的膜PtdCho降解为GPC。PtdCho 1位的酰基部分被不可水解的烷基部分取代，阻止了GPC的降解。烷基酰- ptdcho的积累与细胞增殖的抑制有关，表明其他降解途径不会替代。GPC的形成被溴烯醇内酯阻断，这表明钙非依赖性磷脂酶A(2)是对过量磷脂反应的关键参与者。由于PtdCho通过生物合成转化为PtdEtn，过量的PtdCho导致GPE和GPC的过量产生和排出。因此，一般的膜磷脂稳态是通过CCT和磷脂酶a的相反活性之间的平衡来实现的(2)。
Phosphatidylcholine (PtdCho) is the major membrane phospholipid in mammalian cells, and its synthesis is controlled by the activity of CDP:phosphocholine cytidylyl-transferase (CCT), Enforced CCT expression accelerated the rate of PtdCho synthesis. However, the amount, of cellular PtdCho did not increase as a result of the turnover of both the choline and glycerol components of PtdCho. Metabolic labeling experiments demonstrated that cells compensated for elevated CCT activity by the degradation of PtdCho to glycerophosphocholine (GPC). Phospholipase D-mediated PtdCho hydrolysis and phosphocholine formation were unaffected, Most of the GPC produced in response to excess phospholipid production was secreted into the medium. Cells also degraded the excess membrane PtdCho to GPC when phospholipid formation was increased by exposure to exogenous lysophosphatidylcholine or lysophosphatidylethanolamine. The replacement of the acyl moiety at the 1-position of PtdCho with a non-hydrolyzable alkyl moiety prevented degradation to GPC. Accumulation of alkylacyl-PtdCho was associated with the inhibition of cell proliferation, demonstrating that alternative pathways of degradation will not substitute. GPC formation was blocked by bromoenol lactone, implicating the calcium-independent phospholipase A(2) as a key participant in the response to excess phospholipid. Owing to the fact that PtdCho is biosynthetically converted to PtdEtn, excess PtdCho resulted in overproduction and exit of GPE as well as GPC. Thus, general membrane phospholipid homeostasis is achieved by a balance between the opposing activities of CCT and phospholipase A(2).