Poulos A, Ranieri E, Shankaran P, Callahan J W
Pediatr Res. 1984 Nov;18(11):1088-93. doi: 10.1203/00006450-198411000-00006.
Cultured skin fibroblast homogenates from patients with Niemann-Pick disease Type C, were able to degrade sphingomyelin liposomes at a normal rate. Fibroblasts from patients with Niemann-Pick disease Types A and B were less active (0.08-0.55 versus 0.96-2.93 nmol/h/mg). When fibroblasts were maintained in synthetic media (MCDB-104) devoid of fetal calf serum for a period of 21 days, sphingomyelinase activity measured at pH 3.8 increased in control and Niemann-Pick Type C (up to 15-fold) and in Niemann-Pick Type B (up to 3-fold) while Niemann-Pick Type A showed no significant increase in sphingomyelinase activity. Addition of a protein activator isolated from the spleen of a Type I Gaucher's disease patient stimulated a 2-7.5-fold increase in sphingomyelinase activity in normal, Niemann-Pick Type B and C fibroblasts, while under the same conditions the Niemann-Pick Type A fibroblast enzyme responded poorly. Our data show that the residual sphingomyelinase activity in Niemann-Pick Type A can be differentiated from that present in other phenotypic forms by its lack of response to the Gaucher activator. Furthermore, we can find no evidence to support the view that Niemann-Pick Type C sphingomyelinase differs from the normal enzyme in its response to Gaucher activator.
来自C型尼曼-匹克病患者的培养皮肤成纤维细胞匀浆能够以正常速率降解鞘磷脂脂质体。来自A型和B型尼曼-匹克病患者的成纤维细胞活性较低（分别为0.08 - 0.55与0.96 - 2.93 nmol/h/mg）。当成纤维细胞在不含胎牛血清的合成培养基（MCDB - 104）中培养21天时，在pH 3.8下测得的鞘磷脂酶活性在对照和C型尼曼-匹克病（高达15倍）以及B型尼曼-匹克病（高达3倍）中有所增加，而A型尼曼-匹克病的鞘磷脂酶活性没有显著增加。添加从一名I型戈谢病患者脾脏中分离出的蛋白质激活剂，可使正常、B型和C型尼曼-匹克病成纤维细胞中的鞘磷脂酶活性增加2 - 7.5倍，而在相同条件下，A型尼曼-匹克病成纤维细胞酶的反应较差。我们的数据表明，A型尼曼-匹克病中残留的鞘磷脂酶活性因其对戈谢激活剂缺乏反应，可与其他表型形式中的活性相区分。此外，我们找不到证据支持C型尼曼-匹克病鞘磷脂酶在对戈谢激活剂的反应上与正常酶不同的观点。
