Roles of a new signal transducing enzyme, phospholipase D (PLD) during cellular apoptosis

Phospholipase D （PLD） hydrolyzes phospholipids， especially phosphatidylcholine （PC） to phosphatidic acid （PA） and choline。PA作为第二次信使，可以转换成其他信使分子，例如磷脂酸（LPA）和1，2-二酰甘油（DG）。Recent cDNA cloning studies have revealed the existence of at least two isozymes （PLD1， PLD2） in mammalian cells。对于PLD 1，两种可替代的复制形式，PLD 1a和PLD 1b已识别。再加上这些，PLD （PLDOA）的另一种类型是由不饱和的脂肪酸激活的，而橄榄酸已被建议，但其分子性质还不为人所知。在添加到糖基化磷脂、鞘磷脂酰亚胺是由一种压力信号的变化引起的，包括细胞因子和化学治疗剂。神经胶质素的氢化作用由神经胶质酶在生成的Ceramide中的结果，被归类为差异和凋亡的第二信使。N-acetylsphingosine （C-D22） ... More ），一种可穿透的膜模拟，抑制多种类型的细胞、包括RBL-2 H3细胞、PC 12细胞和C6胶质瘤细胞的PLD活动。在这些细胞的适应性过程中， GTPγ S-依赖PLD在细胞裂解物降解的时间依赖。Moreover，rPLD 1a和rPLD 1b的mRNA水平显示时间依赖性退化。在对比中，rPLD 2的mRNA水平略微增加。在与以上细胞列出的明显对比下， PLD活动在凋亡后被上调，由actinomycin D、TNF-α或H202诱导，Jurkat T细胞主要快速PLDOA。结果发现，即使在静止细胞中PLD产生存活信号的情况下也有一些建议。当对增长或差异信号的反应时，它被激活并增加了该信号的强度。在另一边， apoptotic agent触发死亡信号转换，如良好地关闭生存信号，包括GTPγ S-依赖PLD活动。通过对比，不受管制的PLD激活，被观察到Jurkat T细胞，也导致细胞死亡。Less（低）

Phospholipase D (PLD) hydrolyzes phospholipids, especially phosphatidylcholine (PC) to phosphatidic acid (PA) and choline. PA acts as a second messenger and can be converted to other messenger molecules, such as lysophosphatidic acid (LPA) and 1,2-diacylglycerol (DG). Recent cDNA cloning studies have revealed the existence of at least two isozymes (PLD1, PLD2) in mammalian cells. For PLD1, two alternatively spliced forms, PLD1a and PLD1b have been identified. In addition to these, another type of PLD (PLDOA) which is activated by unsaturated fatty acids such as oleic acid has been suggested, although its molecular nature is not known yet. In addition to glycerophospholipids, sphingomyelin hydrolysis is induced by a variety of stress signals including cytokines and chemotheraputic agents. Hydrolysis of sphingomyelin by sphingomyelinase results in the production of ceramide, which is regarded as a second messenger of differentiation and apoptosis. N-acetylsphingosine (CィイD22ィエD2-ceramide … More ), a membrane-permeable analogue, inhibits PLD activity in several types of cells, including RBL-2H3 cells, PC12 cells and C6 glioma cells. During apoptotic process of these cells, GTPγS-dependent PLD activity in cell lysates decreased time-dependently. Moreover, mRNA levels of rPLD1a and rPLD1b showed time-dependent decreases. In contrast, the mRNA level of rPLD2 slightly increased. In sharp contrast to the cells listed above, PLD activity was upregulated during apoptosis, induced by actinomycin D, TNF-α or H202, of Jurkat T cells which mainly express PLDOA. The results obtained suggest that even in resting cells PLD produces survival signals. In response to growth or differentiation signals, it is activated and increases the strength of this signal. On the other hand, apoptotic agents trigger death signal transduction as well as shutting off survival signals including GTPγS-dependent PLD activity. By contrast, unregulated activation of PLD, as observed in Jurkat T cells, also causes cell death. Less