IkappaBalpha degradation is not a requirement for the X-ray-induced activation of nuclear factor kappaB in normal rat astrocytes and human brain tumour cells.

Abstract:

PURPOSE:To investigate the mechanism of NFkappaB activation by X-rays in normal primary rat astrocytes. MATERIALS AND METHODS:Primary cultures of type I astrocytes generated from the cortex of neonatal rats were exposed to X-rays with and without various kinase inhibitors and a protease inhibitor. The nuclear or cytoplasmic protein extracts were collected at specified times after treatment and analysed for NFkappaB-DNA binding activity and IkappaB protein levels. RESULTS:The NFkappaB-DNA binding activity was induced by X-rays in a dose- and time-dependent manner in the absence of IkappaB protein degradation in astrocytes as well as in the human glioma cell line U-373MG. Whereas a protease inhibitor (calpain inhibitor 1) and a protein kinase C inhibitor (CGP-41251) did not affect X-ray-induced NFkappaB-DNA binding, treatment of astrocytes with the tyrosine kinase inhibitor (erbstatin) completely prevented the increase in NFkappaB activity after irradiation. Erbstatin also reduced the phosphorylation of IkappaBalpha after X-ray exposure. CONCLUSIONS:These results indicate that, in contrast with the more frequently investigated activators of NFkappaB, radiation-induced activation of this transcription factor proceeds in the absence of IkappaBalpha degradation and requires tyrosine phosphorylation.

journal_name

Int J Radiat Biol

authors

Raju U,Gumin GJ,Noel F,Tofilon PJ

doi

10.1080/095530098141195

subject

Has Abstract

pub_date

1998-11-01 00:00:00

pages

617-24

issue

5

eissn

0955-3002

issn

1362-3095

journal_volume

74

pub_type

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