Bioactive Phospholipids Enhance Migration and Adhesion of Human Leukemic Cells by Inhibiting Heme Oxygenase 1 (HO-1) and Inducible Nitric Oxygenase Synthase (iNOS) in a p38 MAPK-Dependent Manner.
Bioactive Phospholipids Enhance Migration and Adhesion of Human Leukemic Cells by Inhibiting Heme Oxygenase 1 (HO-1) and Inducible Nitric Oxygenase Synthase (iNOS) in a p38 MAPK-Dependent Manner.
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DOI：
10.1007/s12015-018-9853-6
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发表时间：
2019-03
影响因子：
4.8
通讯作者：
Ratajczak MZ
中科院分区：
文献类型：
--
作者：
Abdelbaset-Ismail A;Cymer M;Borkowska-Rzeszotek S;Brzeźniakiewicz-Janus K;Rameshwar P;Kakar SS;Ratajczak J;Ratajczak MZ
生物活性磷脂，包括鞘氨醇-1-磷酸（S1 P）、神经酰胺-1-磷酸（C1 P）、溶血磷脂酰胆碱（LPC）及其衍生物溶血磷脂酸（LPA），已经成为调节正常和癌细胞运输的重要介质。虽然S1 P在调节造血细胞迁移中的作用已经得到了很好的证实，但在这项工作中，我们将其生物学效应与C1 P、LPC和LPA的效应进行了比较。我们使用了10个人骨髓和淋巴细胞系以及来自AML患者的原始细胞。我们观察到人类白血病细胞表达功能性磷脂受体，并对p42/44 MAPK和AKT磷酸化的刺激作出反应。我们还发现，生物活性磷脂通过下调HO-1和iNOS的表达以p38 MAPK依赖的方式增强白血病细胞的细胞迁移和粘附，但不影响细胞增殖。与此相反，SB 203580下调p38 MAPK增强HO-1和iNOS的表达，并降低白血病细胞在体外的迁移和接种效率，以重要器官后，在体内注射到免疫缺陷小鼠。基于这些发现，我们证明，除了S1 P，人类白血病细胞也响应C1 P，LPC和LPA。由于生物活性磷脂在体内的促转移作用至少部分是通过下调HO-1和iNOS的表达以p38 MAPK依赖的方式介导的，因此我们建议p38 MAPK抑制剂或HO-1活性刺激剂将在抑制白血病细胞对生物活性磷脂的反应中的扩散中找到应用。
Bioactive phospholipids, including sphingosine-1-phosphate (S1P), ceramide-1-phosphate (C1P), lysophosphatidylcholine (LPC), and its derivative lysophosphatidic acid (LPA), have emerged as important mediators regulating the trafficking of normal and cancer cells. While the role of S1P in regulating migration of hematopoietic cells is well established, in this work we compared its biological effects to the effects of C1P, LPC, and LPA. We employed 10 human myeloid and lymphoid cell lines as well as blasts from AML patients. We observed that human leukemic cells express functional receptors for phospholipids and respond to stimulation by phosphorylation of p42/44 MAPK and AKT. We also found that bioactive phospholipids enhanced cell migration and adhesion of leukemic cells by downregulating expression of HO-1 and iNOS in a p38 MAPK-dependent manner but did not affect cell proliferation. By contrast, downregulation of p38 MAPK by SB203580 enhanced expression of HO-1 and iNOS and decreased migration of leukemic cells in vitro and their seeding efficiency to vital organs in vivo after injection into immunodeficient mice. Based on these findings, we demonstrate that, besides S1P, human leukemic cells also respond to C1P, LPC, and LPA. Since the prometastatic effects of bioactive phospholipids in vivo were mediated, at least in part, by downregulating HO-1 and iNOS expression in a p38 MAPK-dependent manner, we propose that inhibitors of p38 MAPK or stimulators of HO-1 activity will find application in inhibiting the spread of leukemic cells in response to bioactive phospholipids.
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DOI：
10.1042/bj20091087
发表时间：
2010-11-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Khan SY;McLaughlin NJ;Kelher MR;Eckels P;Gamboni-Robertson F;Banerjee A;Silliman CC
通讯作者：
Silliman CC
影响因子：
4.8
作者：
Hu, Xiaojie;Mendoza, Francisco J.;Gibson, Spencer B.
通讯作者：
Gibson, Spencer B.
影响因子：
11.4
作者：
Abdelbaset-Ismail A;Borkowska-Rzeszotek S;Kubis E;Bujko K;Brzeźniakiewicz-Janus K;Bolkun L;Kloczko J;Moniuszko M;Basak GW;Wiktor-Jedrzejczak W;Ratajczak MZ
通讯作者：
Ratajczak MZ
影响因子：
2.6
作者：
Ortlepp, Claudia;Steudel, Christine;Thiede, Christian
通讯作者：
Thiede, Christian
影响因子：
5.2
作者：
Kim, Chihwa;Schneider, Gabriela;Abdel-Latif, Ahmed;Mierzejewska, Kasia;Sunkara, Manjula;Borkowska, Sylwia;Ratajczak, Janina;Morris, Andrew J.;Kucia, Magda;Ratajczak, Mariusz Z.
通讯作者：
Ratajczak, Mariusz Z.