Psychosine cytotoxicity toward rat C6 glioma cells and the protective effects of phorbol ester and dimethylsulfoxide: Implications for therapy in Krabbe disease

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      Psychosine cytotoxicity was tested as to its effects on rat C6 glioma cells. At a low concentration-below 40 μM-psychosine appeared to stimulate cell proliferation. Above the concentration range of 40 μM – 60 μM, however, it showed a cytotoxic effect. When phorbol ester (PDB) or dimethylsulfoxide (DMSO) was supplemented to cultures being exposed to psychosine, the total number of live cells, protein content and CNPase activity dramatically increased as compared with the levels in cultures treated with psychosine alone. The results of these basic studies suggest another approach as to therapy for globoid cell leukodystrophy.

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        • Suzuki K
        • Suzuki Y
        Globoid cell leukodystrophy (Krabbe's disease): deficiency of galactocerebroside-β-galactosidase.
        Proc Natl Acad Sci USA. 1970; 66: 302-309
        • Suzuki K
        • Suzuki Y
        Galactosylceramide lipidosis: globoid cell leukodystrophy (Krabbe's disease).
        in: Stanbury JB Wyngaarden JB Fredrickson DS The metabolic basis of inherited disease. McGraw-Hill, New York1983: 857-880
        • Austin JH
        • Lehfeldt D
        Studies in globoid (Krabbe) leukodystrophy. III. Significance of experimentally produced globoid-like elements in rat white matter and spleen.
        J Neuropathol Exp Neurol. 1965; 24: 265-289
        • Suzuki K
        • Tanaka H
        • Suzuki K
        Studies on the pathogenesis of Krabbe's leukodystrophy—cellular reaction of the brain to exogenous galactosylsphingosine monogalactosyl diglyceride and lactosylceramide.
        in: Volk BW Schneck L Current trends in sphingolipidoses and allied disorders. Plenum Press, New York1976: 99-114
        • Svennerholm L
        • Vanier M-T
        • Mansson J-E
        Krabbe's disease: a galactosylsphingosine (psychosine) lipidosis.
        J Lipid Res. 1980; 21: 53-64
        • Miyatake T
        • Suzuki K
        Globoid cell leukodystrophy: additional deficiency of psychosine galactosidase.
        Biochem Biophys Res Commun. 1972; 48: 538-543
        • Taketomi T
        • Yamakawa T
        Physiological activity of psychosine.
        Jpn J Exp Med (Tokyo). 1964; 34: 255-265
        • Pfeiffer SE
        • Betschart B
        • Cook J
        • Mancini P
        • Morris R
        Glial cell line.
        in: Fedoroff S Hertz L Cell, tissue and organ cultures in neurobiology. Academic Press, New York1977
        • Volpe JJ
        • Fujimoto K
        • Marasa JC
        • Agarawal HC
        Relation of C-6 glial cells in culture to myelin.
        Biochem J. 1975; 152: 701-703
        • Sims NR
        • Carnegie PR
        A rapid assay for 2′, 3′-cyclic nucleotide 3′-phosphohydrolase.
        J Neurochem. 1976; 27: 769-772
        • Sprinkle TJ
        • Wells MR
        • Garner FA
        • Smith DB
        Studies on the Wolfgram high molecular weight CNS myelin proteins: relationship to 2′,3′-cyclic nucleotide 3' phosphodiesterase.
        J Neurochem. 1980; 35: 1200-1208
        • Bignami A
        • Eng L
        • Dahl D
        • Uyeda C
        Localization of the glial acidic protein in astrocytes by immunofluorescence.
        Brain Res. 1972; 43: 429-435
        • Kobayashi T
        • Goto I
        • Yamanaka T
        • Suzuki Y
        • Nakano T
        • Suzuki K
        Infantile and fetal globoid cell leukodystrophy: analysis of galactosylceramide and galactosylsphingosine.
        Ann Neurol. 1988; 24: 517-522
        • Kurihara T
        • Tsukada Y
        2′,3′-Cyclic nucleotide 3′-phosphohydrolase in the developing chick brain and spinal cord.
        J Neurochem. 1968; 15: 827-832
        • Blumberg PM
        • Driedger PE
        • Rossow PW
        Effect of a phorbol ester on transformation-sensitive surface protein of chick fibroblasts.
        Nature. 1976; 264: 446-447
        • Young VW
        • Sekiguchi S
        • Kim MW
        • Kim SU
        A phorbol ester enhances morphological differentiation of oligodendrocytes in culture.
        J Neurosci Res. 1988; 19: 187-194
        • Nishizuka Y
        Studies and perspectives of protein kinase C.
        Science. 1986; 223: 305-311
        • Hannun YA
        • Bell RM
        Functions of sphingolipids and sphingolipid breakdown products in cellular regulation.
        Science. 1989; 243: 500-507
        • Jacob SW
        • Herschier R
        Introductory remarks: dimethylsulfoxide after twenty years.
        Ann NY Acad Sci. 1983; 411: 13-17
        • Sakuragawa N
        • Sato M
        • Yoshida Y
        • Kamo I
        • Arima M
        • Satoyoshi E
        Effects of dimethylsulfoxide on sphingomyelinase in cultured human fibroblasts from Niemann-Pick patients.
        Biochem Biophys Res Commun. 1985; 126: 756-762
        • Igarashi Y
        • Hakomori S
        • Toyokuni T
        • et al.
        Effects of chemically well-defined sphingosine and its N-methyl derivatives on protein kinase C and src kinase activities.
        Biochemistry. 1989; : 6796-6800