Mitogen-activated protein kinases: Specificity of response to dose of ionizing radiation in liver

Abstract

Ionizing radiation is known to activate both the cytotoxic stress-activated kinases (SAPK/JNK, p38) and the cytoprotective mitogen-activated protein kinases (MAPKs, ERKs), which send divergent signals to the nucleus. However, all these kinases could not be activated simultaneously and at all the doses. An attempt has been made in this study to establish the dose and temporal response of these kinases with a view to establish the identity of the transcription factors that remain activated because only these will be translated into an effect. The study indicates that the stress-activated kinases (SAPK/JNK and p38) are activated by very low doses (0.1 Gy) of ionizing radiation. An induction of expression of MKK4, precursor to SAPK and p38, was found at lower doses (0.1-0.5 Gy). However, the cytoprotective ERK2 showed a progressive increase in expression with dose, except at 3 Gy where it shows a marginal decline. The stress-activated kinases show an increased expression or activation at early periods, unlike ERK2, which shows a prolonged response to stimuli. This study reveals that in the in vivo condition there is a chronological order of activation of the kinases and a dose-dependent activation. The activations of the cytoplasmic kinases and the transcription factors, Elk-1 and c-Jun, both show prolonged activation and maximum response at high doses.