Abstract
We studied the effects of SEB on [14C]-choline transport and metabolism of choline containing phospholipids in cultured human kidney proximal tubular (PT) cells. SEB increased the uptake of [14C]-choline in PT cells as a function of toxin concentration, incubation time, and pH. The maximum increase in uptake (3.5–5-fold compared to control) was observed at a toxin concentration of 10 ug/104 cells, at 4 h and at pH 7.4. Two toxins structurally related to SEB, Staphylococcal enterotoxin-A and toxic shock toxin (TST-1) failed to alter [14C]-choline uptake in PT cells, a finding which indicates that SEB-mediated alteration in choline uptake in PT cells has high specificity.
We found that SEB markedly and significantly increased the incorporation of [14C]-choline into phosphatidylcholine, Iysophosphatidylcholine and sphingomyelin, but not into phosphatidylethanolamine. Maximum increase in the incorporation of [14C]-choline into phosphatidlycholine (3-fold compared to control) was observed at 4 h after incubation with toxin. In contrast, SEB did not alter the incorporation of [14C]-choline in phosphatidylethanolamine. The cellular level of phosphatidylcholine was also increased (2-fold compared to control) in PT cells incubated with SEB. This was accompanied by a 3-to-4-fold increase in CTP: phosphocholine, cytidyltransferase activity.
In sum, SEB specifically stimulates phosphatidylcholine synthesis in PT cells by increasing choline uptake or by activating CTP: phosphocholine, cytidyltransferase, or both. We believe this is the first-ever report indicating that a toxin can increase phosphatidylcholine synthesis. This high order of specificity may be in part due to the presence of a glycosphingolipid receptor in PT cells that specifically binds SEB but not SEA or TST-1. Accordingly, it is tempting to speculate that the receptor may somehow be involved in the SEB-mediated regulation of phosphatidylcholine synthesis.
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Abbreviations
- SEB:
-
Staphylococcal entertoxin-B
- SEA:
-
Staphylococcal enterotoxin-A
- TST-1:
-
Toxic shock syndrome toxin-1
- PT:
-
Proximal tubular
- PC:
-
Phosphatidylcholine
- SM:
-
Sphingomyelin
- LPC:
-
Lysophosphatidyl-choline
- CT:
-
Cytidyltransferase
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Khullar, M., Chatterjee, S. Staphylococcal enterotoxin-B (SEB) alters [14C]-choline transport and phosphatidylcholine metabolism in cultured human kidney proximal tubular cells. Mol Cell Biochem 146, 115–120 (1995). https://doi.org/10.1007/BF00944603
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DOI: https://doi.org/10.1007/BF00944603