Differential usage of IκBα and IκBβ in regulation of apoptosis versus gene expression

• n 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-κB in the induction of apoptosis and surface immunoglobulin κ (Igκ) expression in the mouse pre-B cell line 70Z/3. We first showed that 3-CPA-induced apoptosis at doses around 500 μM 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 Igκ expression while 3-CPA had no effect. Further analysis showed that while 3-CPA inhibited breakdown of IκBα, Na-3-CPA inhibited breakdown of IκBβ. In addition, we used a 70Z/3 cell line expressing a dominant negative IκBα (70Z/3ΔNIκBα). The 70Z/3ΔNIκBα 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-κB rescue mechanism. Taken together, our data implicate distinct roles for IκBα and IκBβ in regulating various NF-κB activities.

Ämnesord

NATURVETENSKAP  -- Biologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences (hsv//eng)

Nyckelord

NF-κB

Apoptosis

IκB

N-substituted benzamides

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