Variations among cell lines in the synthesis of sphingolipids in de novo and recycling pathways |
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Authors: | Gillard BK; Clement RG; Marcus DM |
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Institution: | Department of Medicine, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA. |
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Abstract: | There are several pathways for the incorporation of sugars into
glycosphingolipids (GSL). Sugars can be added to ceramide that contains
sphinganine (dihydrosphingosine) synthesized de novo (pathway 1), to
ceramide synthesized from sphingoid bases produced by hydrolysis of
sphingolipids (pathway 2), and into GSL recycling from the endosomal
pathway through the Golgi (pathway 3). We reported previously the
surprising observation that SW13 cells, a human adrenal carcinoma cell
line, synthesize most of their GSL in pathway 2. We now present data on the
synthesis of GSL in four additional cell lines. Approximately 90% of sugar
incorporation took place in pathway 2, and 10% or less in pathway 1, in
human foreskin fibroblasts and NB41A3 neuroblastoma cells. In contrast,
approximately 50-90% of sugar incorporation took place in pathway 1 in
C2C12 myoblasts. The C2C12 cells divide more rapidly and synthesize 10-14
times as much GSL as the other three cell lines. In C6 glioma cells,
approximately 30% of sugar incorporation occurred in pathway 1 and 60% in
pathway 2. There was no relation between the utilization of pathways for
GSL and sphingomyelin synthesis in foreskin fibroblasts and C2C12 cells. In
both cells pathways 1 and 2 each accounted for 50% of incorporation of
choline into sphingomyelin. In five of the six cell lines that we have
studied, most GSL synthesis takes place in pathway 2. We suggest that when
the need for synthesis is relatively low, as in slowly dividing cells, GSL
are synthesized predominantly from sphingoid bases salvaged from the
hydrolytic pathway. When cells are dividing more rapidly, the need for
increased synthesis is met by upregulating the de novo pathway.
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