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

H Narang1, M Krishna

  • 1Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre Trombay, Mumbai, India.

Journal of Radiation Research
|August 12, 2004
PubMed

Insights

Ionizing radiation activates stress-activated kinases at low doses and cytoprotective kinases with increasing doses. This study details the dose and time-dependent activation of these signaling pathways and transcription factors.

Area of Science:

  • Cellular biology
  • Molecular signaling
  • Radiation biology

Background:

  • Ionizing radiation triggers both cytotoxic stress-activated kinases (SAPK/JNK, p38) and cytoprotective mitogen-activated protein kinases (MAPKs, ERKs).
  • These kinase pathways transmit divergent signals to the nucleus, but their activation is dose- and time-dependent.
  • Understanding these responses is crucial for elucidating the downstream effects mediated by transcription factors.

Purpose of the Study:

  • To investigate the dose and temporal response of stress-activated and cytoprotective kinases following ionizing radiation exposure.
  • To identify transcription factors that exhibit sustained activation, correlating with biological effects.
  • To establish the chronological order and dose dependency of kinase activation in vivo.

Main Methods:

  • Exposure of biological systems to varying doses of ionizing radiation (0.1 Gy to 3 Gy).
  • Analysis of the expression and activation levels of key kinases, including SAPK/JNK, p38, and ERK2.
  • Assessment of MKK4 induction and the activation of transcription factors Elk-1 and c-Jun.

Main Results:

  • Stress-activated kinases (SAPK/JNK, p38) were activated by low doses (0.1 Gy) of ionizing radiation.
  • MKK4, a precursor kinase, showed induced expression at lower doses (0.1-0.5 Gy).
  • Cytoprotective ERK2 expression increased progressively with dose, with a slight decrease at 3 Gy, while stress-activated kinases showed early, transient activation, and transcription factors Elk-1 and c-Jun displayed prolonged activation at higher doses.

Conclusions:

  • Ionizing radiation elicits a dose- and time-dependent activation of distinct kinase signaling pathways.
  • A chronological activation order exists for kinases and transcription factors in vivo following radiation exposure.
  • Sustained activation of specific kinases and transcription factors like Elk-1 and c-Jun correlates with higher radiation doses and prolonged cellular responses.

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