Lee Yun-Kyung, Im Young-Jin, Kim Yu-Lee, Im Dong-Soon
Laboratory of Pharmacology, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 609-735, Republic of Korea.
Biochem Biophys Res Commun. 2006 Sep 29;348(3):1116-22. doi: 10.1016/j.bbrc.2006.07.164. Epub 2006 Aug 4.
Calcium is a ubiquitous second messenger controlling a broad range of cellular functions. We previously observed that N,N-dimethyl-D-ribo-phytosphingosine (DMPH) and lysophosphatidylcholine (LPC) induced Ca2+ influx across the plasma membrane in U937 monocytes. In this study, we characterized the Ca2+ influx induced by DMPH and LPC. L-type voltage-gated Ca2+ channel blockers, verapamil and nifedipine, significantly reduced LPC-induced Ca2+ influx, but not DMPH-induced one. On the other hand, non-specific Ca2+ channel blockers, Ga3+ and La3+, considerably reduced DMPH- and LPC-induced Ca2+ influx. Preincubation of the cells with forskolin enhanced DMPH-induced Ca2+ influx, however, LPC-induced Ca2+ influx was not affected by the treatment. The enhancement by forskolin was blocked by KT5720, a PKA inhibitor. We also confirmed the presence of TRPM7 and absence of TRPM3 in U937 cells. Therefore, our characterization of Ca2+ influx in U937 human monocytes shows the presence of two different types of Ca2+ channels modulated by lysolipid molecules, DMPH and LPC. LPC may induce Ca2+ influx via L-type Ca2+ channels and DMPH seems to induce Ca2+ influx through TRPM7 in U937 human monocytes.
钙是一种普遍存在的第二信使,控制着广泛的细胞功能。我们之前观察到,N,N-二甲基-D-核糖神经鞘氨醇(DMPH)和溶血磷脂酰胆碱(LPC)可诱导U937单核细胞跨质膜的Ca2+内流。在本研究中,我们对DMPH和LPC诱导的Ca2+内流进行了表征。L型电压门控Ca2+通道阻滞剂维拉帕米和硝苯地平显著降低了LPC诱导的Ca2+内流,但对DMPH诱导的Ca2+内流没有影响。另一方面,非特异性Ca2+通道阻滞剂Ga3+和La3+显著降低了DMPH和LPC诱导的Ca2+内流。用福斯可林预孵育细胞可增强DMPH诱导的Ca2+内流,然而,LPC诱导的Ca2+内流不受该处理的影响。福斯可林的增强作用被PKA抑制剂KT5720阻断。我们还证实了U937细胞中存在TRPM7且不存在TRPM3。因此,我们对U937人单核细胞中Ca2+内流的表征显示,存在两种受溶血脂质分子DMPH和LPC调节的不同类型的Ca2+通道。在U937人单核细胞中,LPC可能通过L型Ca2+通道诱导Ca2+内流,而DMPH似乎通过TRPM7诱导Ca2+内流。