Neutral/alkaline and acid ceramidase activities are actively released by murine endothelial cells
Neutral/alkaline and acid ceramidase activities are actively released by murine endothelial cells
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DOI：
10.1006/bbrc.2000.3370
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发表时间：
2000-09-07
影响因子：
3.1
通讯作者：
Bruni, P
中科院分区：
文献类型：
--
作者：
Romiti, E;Meacci, E;Bruni, P
神经酰胺酶（CDase）在神经脂代谢中发挥关键作用，将神经酰胺水解成鞘氨醇。在这里，我们报道了小鼠内皮细胞、巨噬细胞和人成纤维细胞都能够在培养基中释放酸性和中性/碱性CDase活性。内皮细胞具有最高的细胞和分泌性cdase的比活性，蛋白质合成抑制剂环已亚胺降低了这两种酶的活性，但放线菌素D阻断RNA转录不受影响，酸性和中性/碱性cdase的释放也被brefeldin A（一种破坏高尔基体的真菌代谢物）减少。值得注意的是，用缓激肽处理内皮细胞导致中性/碱性CDase释放显著增加，而非酸性CDase释放。该报告是内皮细胞存在构成性和受调节的CDase活性释放的第一个证据。鉴于已知这些细胞分泌鞘磷脂酶的能力，这一发现提示CDase可能参与细胞外鞘磷脂代谢，目前已知鞘磷脂代谢在动脉粥样硬化中起作用，并可能参与其他生理或病理事件。(C) 2000年学术出版社。
Ceramidases (CDase(s)) play a key role in sphingolipid metabolism by hydrolyzing ceramide into sphingosine. Here we report that murine endothelial cells, macrophages, and human fibroblasts are all able to release acid as well as neutral/alkaline CDase activities in the culture medium. Endothelial cells were characterized by the highest specific activity of cellular as well as secreted CDases, The release of both enzymatic activities was reduced by protein synthesis inhibitor cycloheximide but was unaffected by the blocking of RNA transcription with actinomycin D, The discharge of acid and neutral/alkaline CDases was also diminished by brefeldin A, a fungal metabolite which disrupts Golgi apparatus. Remarkably, treatment of endothelial cells with bradykinin resulted in a significant increase of neutral/alkaline but not acid CDase release. This report represents the first evidence for the existence of constitutive and regulated release of CDase activities by endothelial cells. In view of the known ability of these cells to secrete sphingomyelinase, this finding suggests that CDase may participate in extracellular sphingomyelin metabolism which is presently known to have a role in atherogenesis and could be involved in other physiological or pathological events. (C) 2000 Academic Press.