Phosphatidic acid stimulates inositol 1,4,5-trisphosphate production in adult cardiac myocytes.
Phosphatidic acid stimulates inositol 1,4,5-trisphosphate production in adult cardiac myocytes.
复制标题
磷脂酸刺激成人心肌细胞产生肌醇 1,4,5-三磷酸。
DOI：
10.1161/01.res.72.3.701
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发表时间：
1993
影响因子：
20.1
通讯作者：
Corr,PB
中科院分区：
文献类型：
--
作者：
Kurz,T;Wolf,RA;Corr,PB
磷脂酸的细胞含量可以响应几种激动剂而增加，或者通过磷脂酶 C 催化磷脂水解后二酰甘油的磷酸化，或者直接通过磷脂酶 D 的激活。尽管先前的研究表明磷脂酸的产生仅是调节二酰甘油细胞浓度的一种手段，但最近的研究表明磷脂酸也可以直接调节多种细胞功能。因此，本研究旨在评估磷脂酸是否可以刺激完整成年兔心室肌细胞中的心脏磷脂酶 C。肌醇 1,4,5-三磷酸 [Ins (1,4,5)P3] 的质量通过特异性和灵敏的结合蛋白测定法确定，并使用阴离子交换色谱法直接质量测量来分离选定的肌醇磷酸盐，并使用气相色谱法和质谱法定量肌醇单磷酸 (IP1)、肌醇二磷酸 (IP2)、肌醇三磷酸 (IP3) 和肌醇四磷酸（IP4）。磷脂酸 (10(-9)-10(-6) M) 引起 Ins (1,4,5)P3 积累的快速浓度依赖性增加，刺激 30 秒时峰值增加四到五倍； 50%最大刺激所需的浓度为4.4 x 10(-8) M。各个磷酸肌醇的时间进程表明，响应磷脂酸刺激，IP3、IP4、IP2和IP1的质量连续增加。在细胞外钙不存在或细胞外EGTA (10(-3) M)存在的情况下，响应磷脂酸的Ins(1,4,5)P3的产生没有改变。因此，这些发现表明磷脂酸是成人心室肌细胞中磷酸肌醇生成的有效激活剂。（摘要截短为 250 字）
The cellular content of phosphatidic acid can increase in response to several agonists either by phosphorylation of diacylglycerol after phospholipase C-catalyzed hydrolysis of phospholipids or directly through activation of phospholipase D. Although previous findings indicated that the generation of phosphatidic acid was exclusively a means of regulation of the cellular concentration of diacylglycerol, more recent studies have indicated that phosphatidic acid may also directly regulate several cellular functions. Accordingly, the present study was performed to assess whether phosphatidic acid could stimulate cardiac phospholipase C in intact adult rabbit ventricular myocytes. The mass of inositol 1,4,5-trisphosphate [Ins (1,4,5)P3] was determined by a specific and sensitive binding protein assay and by direct mass measurement using anion exchange chromatography for separation of selected inositol phosphates and gas chromatography and mass spectrometry for quantification of inositol monophosphate (IP1), inositol bisphosphate (IP2), inositol trisphosphate (IP3), and inositol tetrakisphosphate (IP4). Phosphatidic acid (10(-9)-10(-6) M) elicited a rapid concentration-dependent increase in Ins (1,4,5)P3 accumulation, with the peak fourfold to fivefold increase at 30 seconds of stimulation; the concentration required for 50% of maximal stimulation was 4.4 x 10(-8) M. The time course of individual inositol phosphates indicated a successive increase in the mass of IP3, IP4, IP2, and IP1 in response to stimulation with phosphatidic acid. The production of Ins (1,4,5)P3 in response to phosphatidic acid was not altered in the absence of extracellular calcium or in the presence of extracellular EGTA (10(-3) M). Thus, these findings indicate that phosphatidic acid is a potent activator of inositol phosphate production in adult ventricular myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)