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See detailOptimization of stress response through the nuclear receptor-mediated cortisol signalling network
Kolodkin, Alexey UL; Sahin, Nilgun; Phillips, Anna et al

in Nature Communications (2013), 4

It is an accepted paradigm that extended stress predisposes an individual to pathophysiology. However, the biological adaptations to minimize this risk are poorly understood. Using a computational model ... [more ▼]

It is an accepted paradigm that extended stress predisposes an individual to pathophysiology. However, the biological adaptations to minimize this risk are poorly understood. Using a computational model based upon realistic kinetic parameters we are able to reproduce the interaction of the stress hormone cortisol with its two nuclear receptors, the high-affinity glucocorticoid receptor and the low-affinity pregnane X-receptor. We demonstrate that regulatory signals between these two nuclear receptors are necessary to optimize the body’s response to stress episodes, attenuating both the magnitude and duration of the biological response. In addition, we predict that the activation of pregnane X-receptor by multiple, low-affinity endobiotic ligands is necessary for the significant pregnane X-receptor-mediated transcriptional response observed following stress episodes. This integration allows responses mediated through both the high and low-affinity nuclear receptors, which we predict is an important strategy to minimize the risk of disease from chronic stress. [less ▲]

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See detailNuclear receptors as controlling factors in chemical metabolism: Determination of regulatory signal network crucial for co-ordinating cellular response to chemicals
Kolodkin, Alexey UL; Phillips, Anna; Hood, Steve R. et al

in Drug Metabolism Reviews (2010), 42(1), 279-280

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