Mathematical modeling of heat shock protein synthesis in response to temperature change

Abstract

To cite this version:Zuzanna Szymańska, Maciej Zylicz. Mathematical modeling of heat shock protein synthesis in response to temperature change. Journal of Theoretical Biology, Elsevier, 2009, 259 (3) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A c c e p t e d m a n u s c r i p t AbstractOne of the most important questions in cell biology is how cells cope with rapid changes in their environment. The range of common molecular responses includes a dramatic change in the pattern of gene expression and the elevated synthesis of so called heat shock (or stress) proteins (HSPs). Induction of HSPs increases cell survival under stress conditions [9]. In this paper we propose a mathematical model of heat shock protein (HSP) synthesis induced by an external temperature stimulus. Our model consists of a system of nine nonlinear ordinary differential equations describing the temporal evolution of the key variables involved in the regulation of HSP synthesis. Computational simulations of our model are carried out for different external temperature stimuli. We compare our model predictions with experimental data for three different cases -one corresponding to heat shock, the second corresponding to slow heating conditions and the third corresponding to a short heat shock (lasting about 40 minutes). We also present our model predictions for heat shocks carried out up to different final temperatures and finally we present a new hypothesis concerning the molecular response to stress that explains some phenomena observed in experiments.

Modeling the inflammatory response in the hypothalamus ensuing heat stroke: Iterative cycle of model calibration, identifiability analysis, experimental design and data collection

“…Furthermore we neglected the impact of ROS and tested the hypothesis that immune responses ensuing heat stroke are mainly mediated by denatured proteins. Denaturation of proteins can occur at temperatures as low as 37-38°C which stimulates the expression of HSPs through activation of HSF-1 (transcription factor of HSPs) [4,13,14]. Peper et al [14] has shown that the denaturation process of proteins is exponential in T c .…”

Sensing the Heat Stress by Mammalian Cells

“…We were interested in the hsp70 promoter activity because our molecular construct is a Hsp70-GFP fusion gene transfected in Chinese hamster ovary (CHO) cells, as described in [5]. However, two other architectures from [3,4], use a different input for the temperature stress, an input that was proposed for the first time in a computational network by [1]. It is thus important to compare different heat shock network architectures.…”

“…The network from [2] is represented in black, from [3] in red and from [4] in green. HSP:HSF denotes HSP bound to HSF and similar for all other complexes.…”

“…In [3,4] the temperature does not act through a kinase module, but directly on the proteins as a whole. No distinction was made between different families of proteins from the cells.…”

“…The proteins were grouped in two classes: misfolded by the heat shock or correctly folded. Following [1] the fraction of the misfolded proteins, as a function of temperature, used in [3,4] is…”