Utilization of exogenously supplied sphingosine analogues for sphingolipid biosynthesis in Chinese hamster ovary and mouse LM cell fibroblasts.

Ladenson, Ruth C.; Monsey, John; Allin, J; Silbert, David F.

doi:10.1016/s0021-9258(18)53007-6

Cited by 14 publications

(1 citation statement)

References 32 publications

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“…Sphingomyelin metabolism, therefore, also exists in nuclei, and the modulation of nuclear sphingomyelinase (Tamiya-Koizumi et al, 1989) may regulate the intranuclear levels of free sphingosine. Although it has been shown that exogenously added sphingosine and its analogues that enter cells are not further degraded, but are utilized intact for the synthesis of sphingomyelin and glycolipids (Ladenson et al, 1993), it is not clear whether exogenously added sphingosine can enter into the nucleus. However, it has been suggested that the facility by which sphingosine can undergo rapid movement across membranes and compartments (Hope & Cullis, 1987) allows it to easily relocate to other parts of the cell from its site of generation (Wilson et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

Sphingosine Inhibits the Synthesis of RNA Primers by Primase in vitro

Simbulan¹,

Tamiya‐Koizumi²,

Suzuki³

et al. 1994

Biochemistry

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We have previously shown the presence of sphingomyelin and sphingomyelinase in cell nuclei, suggesting that they may play a role in the intranuclear production of sphingosine, a potent bioactive molecule modulating diverse cellular functions. In the present study, the direct effects of sphingosine (C18:1) on the activity of DNA replication/repair polymerases were studied in vitro. Sphingosine had no effect on DNA polymerases alpha and beta and slightly inhibited DNA polymerases gamma, delta, and epsilon. In contrast, sphingosine strongly inhibited the activity of primase in a dose-dependent manner. On the other hand, dihydrosphingosine (C18:0), glycolipids, sphingomyelin, and ceramide had no effect on primase activity. Sphingosine equally inhibited the activity of primase complexed with DNA polymerase alpha, as well as its free form, with a Ki value of 4 microM. A gel-retardation analysis showed that the binding of primase with 32P-labeled template DNA was suppressed by sphingosine. Inhibition by sphingosine was competitive with the DNA template, but not with the substrate NTPs. After product analysis, a dose-dependent decrease in the amount of RNA primer products, consisting mainly of 10- and 11-mers, was observed in the presence of sphingosine, indicating that it inhibits the synthesis of RNA primers by primase. Sphingosine, however, had no effect on T7 RNA polymerase.

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