Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene
Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene
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DOI：
10.1074/jbc.271.31.18431
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发表时间：
1996-08-02
影响因子：
4.8
通讯作者：
Tabas, I
中科院分区：
文献类型：
--
作者：
Schissel, SL;Schuchman, EH;Tabas, I
哺乳动物鞘磷脂酶参与许多重要的生理和病理生理过程。虽然已经鉴定和研究了几种哺乳动物鞘磷脂酶，但其中之一，最初在胎牛血清中发现的酸性Zn 2+刺激的鞘磷脂酶（Zn-SMase），自从7年前首次也是唯一的报道以来，很少受到关注。我们现在表明，锌-SMase活性分泌的人类和小鼠巨噬细胞，人类皮肤成纤维细胞，小胶质细胞，和其他几种细胞在培养过程中，并显着上调人类单核细胞分化为巨噬细胞。值得注意的是，来自小鼠的腹膜巨噬细胞（其中酸性SMase基因已经通过同源重组被破坏）不分泌Zn-SMase活性，表明该酶和不依赖于Zn的细胞内溶酶体SMase来自相同的基因。此外，来自A型和B型尼曼-匹克病患者的皮肤成纤维细胞（已知其缺乏溶酶体SMase活性），在其条件培养基中也缺乏Zn-SMase活性。用编码溶酶体SMase的cDNA稳定转染的中国仓鼠卵巢细胞大量过表达细胞溶酶体SMase和分泌的Zn-SMase活性。因此，Zn-SMase的产生独立于选择性剪接，这表明了一个翻译后过程。总之，多种细胞类型分泌Zn-SMase活性，其来自与溶酶体SMase相同的基因。这种分泌的酶可能在涉及细胞外鞘磷脂水解的生理和病理生理过程中发挥作用。
Mammalian sphingomyelinases have been implicated in many important physiological and pathophysiological processes. Although several mammalian sphingomyelinases have been identified and studied, one of these, an acidic Zn2+-stimulated sphingomyelinase (Zn-SMase) originally found in fetal bovine serum, has received little attention since its first and only report 7 years ago. We now show that Zn-SMase activity is secreted by human and murine macrophages, human skin fibroblasts, microglial cells, and several other cells in culture and is markedly up-regulated during differentiation of human monocytes to macrophages. Remarkably, peritoneal macrophages from mice in which the acid SMase gene had been disrupted by homologous recombination secreted no Zn-SMase activity, indicating that this enzyme and the intracellular lysosomal SMase, which is Zn-independent, arise from the same gene, Furthermore, skin fibroblasts from patients with types A and B Niemann-Pick disease, which are known to lack lysosomal SMase activity, also lack Zn-SMase activity in their conditioned media. Chinese hamster ovary cells stably transfected with a cDNA encoding lysosomal SMase massively overexpress both cellular lysosomal SMase and secreted Zn-SMase activities. Thus, Zn-SMase arises independently of alternative splicing, suggesting a post-translational process. In summary, a wide variety of cell types secrete Zn-SMase activity, which arises from the same gene as lysosomal SMase. This secreted enzyme may play roles in physiological and pathophysiological processes involving extracellular sphingomyelin hydrolysis.