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.
Dawson
G
G
Department of Pediatrics, University of Chicago, IL 60637, USA. dawg@midway.uchicago.edu
Kilkus
J
J
Schieven
G L
GL
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