Differential usage of IkappaBalpha and IkappaBbeta in regulation of apoptosis versus gene expression.
In this study we use the N-substituted benzamides declopramide (3-CPA) and N-acetyl declopramide (Na-3-CPA) to investigate the involvement of the transcription factor NF-kappaB in the induction of apoptosis and surface immunoglobulin kappa (Igkappa) expression in the mouse pre-B cell line 70Z/3. We first showed that 3-CPA-induced apoptosis at doses around 500 microM and that the 3-CPA-induced apoptosis could be suppressed by over-expression of the Bcl-2 protein. Na-3-CPA was shown to be non-apoptotic at doses up to 1-2 mM. On the other hand, Na-3-CPA inhibited LPS-induced Igkappa expression while 3-CPA had no effect. Further analysis showed that while 3-CPA inhibited breakdown of IkappaBalpha, Na-3-CPA inhibited breakdown of IkappaBbeta. In addition, we used a 70Z/3 cell line expressing a dominant negative IkappaBalpha (70Z/3(deltaNIkappaBalpha)). The 70Z/3(deltaNIkappaBalpha) cell line was shown to be more sensitive to apoptosis and cytotoxicity induced by 3-CPA as well as by LPS, probably due to a defect in NF-kappaB rescue mechanism. Taken together, our data implicate distinct roles for IkappaBalpha and IkappaBbeta in regulating various NF-kappaB activities.
Lindgren
Hanna
H
Section for Immunology, BMC I:13, Department of Cell and Molecular Biology, Lund University, S-221 84 Lund, Sweden.
Olsson
Anders R
AR
Pero
Ronald W
RW
Leanderson
Tomas
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001402:B-Lymphocytes / Q000502:physiology; D002460:Cell Line; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism*; D007136:Immunoglobulins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011342:Procainamide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism
C083487:I kappa B beta protein; D020672:I-kappa B Proteins; C014609:IgK; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D000072000:NF-KappaB Inhibitor alpha; C072799:declopramide; D011342:Procainamide