A systematic approach in analyzing sustained oscillations in an NF-kB signal transduction pathway system

摘要

Oscillation phenomenon is very common in biological systems. It is crucial to study oscillatory behaviors to understand gene regulation functions. Model-based analysis in combination with experimental study provides a new and systematic way to investigate biological oscillations. The nuclear factor-kB (NF-kB) signaling is an important signaling pathway that is involved in a variety of cellular processes including immune response, inflammation, and apoptosis. Recent studies revealed damped oscillations of NF-kB activity both experimentally and computationally, etc. In this work, based on a differential equation model, bifurcation analysis was used to examine whether it was possible for this system to produce sustained oscillations (limit cycle oscillations) rather than damped oscillations. Both one- and two-parameter bifurcation analyses have been performed and it was found that certain conditions could possibly result in sustained oscillations of nuclear NF-kB activity. The parameter regimes corresponding to such oscillations were calculated with this method.