Levy B D, Serhan C N
Center for Experimental Therapeutics and Reperfusion Injury, Department of Internal Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts, 02115, USA.
Biochem Biophys Res Commun. 2000 Sep 7;275(3):739-45. doi: 10.1006/bbrc.2000.3371.
To determine the relationship of polyisoprenyl phosphate (PIPP) remodeling and signaling to the activation state of human neutrophils (PMN), we examined the impact of leukotriene B(4) (LTB(4)) on the conversion of a unique bioactive isoprenoid (presqualene diphosphate: PSDP), recently identified as a novel endogenous signaling molecule. LTB(4) initiated rapid decrements in total PSDP that were concurrent with the respiratory burst (e.g., O(-2) formation). PSDP was identified in nuclear (39%)-, granule (36%)-, and plasma membrane (16%)-containing fractions of PMN. LTB(4) receptor (BLT) activation led to a decrease in nuclear PSDP and concomitant increase in granule-associated PSDP. In addition, PMN nuclei displayed PSDP associated with chromatin as established by mass spectrometry. Together, these results indicate that PSDP is present in membranes and receptor activation rapidly initiates subcellular PIPP remodeling (i.e., conversion) and distribution predominantly to granule membranes. Moreover, identification of nuclear PSDP provides the basis for novel roles for PIPP and PSDP in nuclear-associated signaling events.
为了确定聚异戊二烯磷酸酯（PIPP）重塑和信号传导与人类中性粒细胞（PMN）激活状态之间的关系，我们研究了白三烯B4（LTB4）对一种独特的生物活性类异戊二烯（前鲨烯二磷酸：PSDP）转化的影响，该物质最近被鉴定为一种新型内源性信号分子。LTB4引发了总PSDP的快速减少，这与呼吸爆发（例如，O₂形成）同时发生。PSDP在PMN的含核（39%）、颗粒（36%）和质膜（16%）的组分中被鉴定出来。LTB4受体（BLT）激活导致核PSDP减少，同时颗粒相关PSDP增加。此外，通过质谱确定PMN细胞核显示出与染色质相关的PSDP。总之，这些结果表明PSDP存在于膜中，受体激活迅速启动亚细胞PIPP重塑（即转化），并主要分布到颗粒膜。此外，核PSDP的鉴定为PIPP和PSDP在核相关信号事件中的新作用提供了基础。
