Staphylococcal enterotoxin-B (SEB) alters [14C]-choline transport and phosphatidylcholine metabolism in cultured human kidney proximal tubular cells |
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Authors: | M Khullar S Chatterjee |
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Institution: | (1) Department of Pediatrics, Johns Hopkins University, School of Medicine, 600 N. Wolfe Street, CMSC 604, 21287-3654 Baltimore, Maryland, USA |
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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.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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Keywords: | kidney proximal tubular cells staphylococcal enterotoxin-b phosphatidylcholine |
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