Summary
Sphingomyelinase activity in cultured skin fibroblasts from a fetus affected with infantile-type Niemann-Pick disease was 0.5% of control activity; the activities in cells from two patients with adult-type disease (Cases 2 and 3) were 5.0% and 59.0%.
Sphingomyelinase activity was separated into three peaks (I–III) by isoelectric focusing. The isoelectric points were 4.5, 4.9, and 5.2 for peaks I, II, and III, respectively. The three peaks in the Case 2 cells were drastically reduced; only a very small peak could be distinguished (pI of 4.7). On the other hand, three peaks were observed in the Case 3 cells. Peak I had a pI of 4.4, peak II a pI of 4.7, and peak III a pI of 5.2. Peak I was found at near normal level, but both peaks II and III were markedly reduced.
Sphingomyelinase in the peak I fraction obtained from isoelectric focusing in Case 3 cells was found to have the same Km value as that in control cells.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Besley, G. T. N.: Sphingomyelinase defect in Niemann-Pick disease, type C, fibroblasts. FEBS Lett. 80, 71–74 (1977)
Callahan, J. W., Khalil, M., Gerrie, J.: isoenzymes of sphingomyelinase and the genetic defect in Niemann-Pick disease, type C. Biochem. Biophys. Res. Commun. 58, 384–390 (1974)
Callahan, J. W., Khalil, M., Philippart, M.: Sphingomyelinases in human tissues. II. Absence of a specific enzyme from liver and brain of Niemann-Pick disease, type C. Pediatr. Res. 9, 908–913 (1975)
Callahan, J. W., Khalil, M.: Sphingomyelinases in human tissues. III. Expression of Niemann-Pick disease in cultured skin fibroblasts. Pediatr. Res. 9, 914–918 (1975)
Callahan, J. W., Khalil, M.: Sphingomyelinases and the genetic defects in Niemann-Pick disease. Adv. Exp. Med. Biol. 68, 367–378 (1976)
Fredrickson, D. S., Sloan, H. R.: Sphingomyelin lipidose: Niemann-Pick disease. The metabolic basis of inherited disease. J. B. Stanbury, J. B. Wyngaarden, D. S. Fredrickson, eds., pp. 783–807. New York: McGraw-Hill 1972
Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193, 265–275 (1951)
Minami, R., Suzuki, M., Kudoh, T., Sato, S., Oyanagi, K., Nakao, T., Sukegawa, K., Orii, T.: α-L-iduronidase activity in established lymphoblastoid cells from patients with Hurler and Scheie syndromes transformed by Epstein-Barr virus. Tohoku J. Exp. Med. 122, 393–396 (1977)
Norman, R. M., Forrester, R. M., Tingey, A. H.: The juvenile form of Niemann-Pick disease. Arch. Dis. Child. 42, 91–96 (1967)
Orii, T., Sukegawa, K., Minami, R., Matsuura, Y., Horino, K., Maeda, E., Kakao, T., Kushida, H.: Atypical Hurler syndrome without α-L-iduronidase deficiency. Tohoku J. Exp. Med. 120, 113–123 (1976)
Orii, T.: Genetic heterogeneity in GM1-gangliosidosis and adult Niemann-Pick disease. The proceedings of the symposium sponsored by the malnutrition panels of The United States-Japan cooperative medical sciences program, pp. 146–158. Sendai (Japan): 1976
Sloan, H. R., Uhlendorf, B. W., Kanfer, J. N., Brady, R. O., Fredrickson, D. S.: Deficiency of sphingomyelin-cleaving enzyme activity in tissue cultures derived from patient with Niemann-Pick disease. Biochem. Biophys. Res. Commun. 34, 582–588 (1969)
Sloan, H. R.: Sphingomyelinase from human liver (sphingomyelin cholinephosphohydrolase). Methods in enzymology, S. P. Colowiek, ed., pp. 874–879. New York: Academic Press 1972
Stoffel, W., Lekim, D., Tschung, T. S.: A simple chemical method for labelling phosphatidylcholine and sphingomyelin in the choline moiety. Hoppe Seylers Z. Physiol. Chem. 352, 1058–1064 (1971)
Wenger, D. A., Barth, G., Githens, J. H.: Nine cases of sphingomyelin lipidosis, a new variant in Spanish-American children. Juvenile variant of Niemann-Pick disease with foamy and sea-blue histiocytes. Am. J. Dis. Child. 131, 955–961 (1977)
Wiedemann, H. R., Debuch, H., Lennert, K., Caesar, R., Blümcke, S., Harms, D., Toklsdorf, M., Seng, P. N., Korenke, H. D., Gerken, H., Freitag, F., Dörner, K. L.: Infantile-juvenile, slowly progressive lipidosis. Belonging to the sphingomyelinoses (Niemann-Pick) — a new type? Z. Kinderheilk. 112, 187–225 (1972)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Minami, R., Matsuura, Y., Nakamura, F. et al. Sphingomyelinase activities in cultured skin fibroblasts from patients with Niemann-Pick disease. Hum Genet 47, 159–167 (1979). https://doi.org/10.1007/BF00273198
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00273198