Plasma membrane form of phosphatidate phosphohydrolase: a possible role in signal transduction during liver fibrogenesis.
Plasma membrane form of phosphatidate phosphohydrolase: a possible role in signal transduction during liver fibrogenesis.
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磷脂酸磷酸水解酶的质膜形式：肝纤维形成过程中信号转导的可能作用。
DOI：
10.1042/cs0850281
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发表时间：
1993
期刊：
影响因子：
6
通讯作者：
S. Yeaman
中科院分区：
文献类型：
--
作者：
C. Day;A. Burt;A. Brown;M. Bennett;D. J. Farrell;O. James;S. Yeaman
1.几种在肝再生和纤维化中重要的生长因子通过受体/G蛋白偶联机制刺激质膜中的磷脂酶D，导致磷脂酰胆碱水解为磷脂酸。磷脂酸可被磷脂酸磷酸水解酶进一步水解为甘油二酯。磷脂酸和甘油二酯可以作为“第二信使”，调节磷脂酸磷酸水解酶的活性可以控制它们之间的平衡。2.磷脂酸磷酸水解酶的一种形式，位于质膜上，对N-乙基马来酰亚胺的抑制不敏感，最近已被鉴定为不同于“代谢”形式，其存在于细胞溶胶和微粒体中，对N-乙基马来酰亚胺敏感。3.我们已经研究了这一假设，即再生和纤维化之间的平衡，在一定程度上，通过其对磷脂酸/甘油二酯比的影响，由质膜磷脂酸磷酸水解酶的活性决定。N-乙基马来酰亚胺不敏感和敏感的磷脂酸磷酸水解酶活性测定在三个肝脏条件下，其特征在于再生和/或纤维化：酒精性肝病在人类（再生和纤维化）和大鼠肝脏后，无论是急性四氯化碳-4诱导的损伤（再生）或胆总管结扎（纤维化）。4.在酒精性肝病患者中，肝活检组织中N-乙基马来酰亚胺不敏感的磷脂酸磷酸水解酶活性较高（5.82 +/- 0.3 nmol Pi min-1 mg-1蛋白，n = 19）（2.17 +/- 0.2，n = 23）或接受常规胆囊切除术的健康受试者的楔形活检（2.16 +/- 0.5，n = 6）。（250字处删节）
1. Several growth factors important in liver regeneration and fibrosis stimulate phospholipase D in plasma membranes via a receptor/G-protein-coupled mechanism resulting in hydrolysis of phosphatidylcholine to phosphatidate. Phosphatidate can be further hydrolysed to diacylglycerol by phosphatidate phosphohydrolase. Phosphatidate and diacylglycerol can act as 'second-messengers' and regulation of phosphatidate phosphohydrolase activity could control the balance between them. 2. A form of phosphatidate phosphohydrolase, located in the plasma membrane and insensitive to inhibition by N-ethylmaleimide, has recently been identified that is distinct from the 'metabolic' form, which is present in the cytosol and microsomes and is sensitive to N-ethylmaleimide. 3. We have investigated the hypothesis that the balance between regeneration and fibrosis is, in part, determined by the activity of plasma membrane phosphatidate phosphohydrolase through its effect on the phosphatidate/diacylglycerol ratio. N-Ethylmaleimide-insensitive and -sensitive phosphatidate phosphohydrolase activities were measured in three hepatic conditions characterized by regeneration and/or fibrosis: alcoholic liver disease in humans (regeneration and fibrosis) and rat livers after either acute CCl-4-induced injury (regeneration) or common bile duct ligation (fibrosis). 4. In patients with alcoholic liver disease, N-ethylmaleimide-insensitive phosphatidate phosphohydrolase activity was higher in cirrhotic biopsies (5.82 +/- 0.3 nmol of Pi min-1 mg-1 of protein, n = 19) than in non-cirrhotic biopsies (2.17 +/- 0.2, n = 23) or in wedge biopsies from healthy subjects undergoing routine cholecystectomy (2.16 +/- 0.5, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)