Selective phosphotyrosine phosphatase inhibition and increased ceramide formation is associated with B-cell death by apoptosis.
Bis(maltolato)oxovanadium(IV) (BMOV), a protein phosphotyrosine phosphatase inhibitor, selectively induced apoptosis (as quantitated by TUNEL staining) in a B-cell line (Ramos) but not in a T-cell line (Jurkat). The pattern of BMOV-induced protein tyrosine phosphorylation was different in B-cells versus T-cells. Further, BMOV induced a 2-fold increase in ceramide levels in B-cells but not in T-cells and this resembled the ceramide increase following activation of the B-cell antigen receptor. A 2-fold increase in the ratio of ceramide to sphingomyelin in B-cells treated with BMOV suggested that sphingomyelinase activation was the result of the sustained tyrosine phosphorylation of specific proteins and activated the cell death pathway.
Department of Pediatrics, University of Chicago, IL 60637, USA. dawg@midway.uchicago.edu
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Dawson
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Kilkus
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Schieven
D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002460:Cell Line; D002518:Ceramides / Q000096:biosynthesis*; D006801:Humans; D020287:In Situ Nick-End Labeling; D019169:Jurkat Cells; D009928:Organ Specificity; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011753:Pyrones / Q000494:pharmacology*; D013109:Sphingomyelins / Q000378:metabolism; D013110:Sphingosine / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology*
D002518:Ceramides; D011753:Pyrones; D013109:Sphingomyelins; D019000:Phosphotyrosine; C074212:bis(maltolato)oxovanadium(IV); D014638:Vanadates; D017027:Protein Tyrosine Phosphatases; D013110:Sphingosine