Abstract
BackgroundCells have the ability to respond and adapt to environmental changes through activation of stress-activated protein kinases (SAPKs). Although p38 SAPK signalling is known to participate in the regulation of gene expression little is known on the molecular mechanisms used by this SAPK to regulate stress-responsive genes and the overall set of genes regulated by p38 in response to different stimuli.ResultsHere, we report a whole genome expression analyses on mouse embryonic fibroblasts (MEFs) treated with three different p38 SAPK activating-stimuli, namely osmostress, the cytokine TNFα and the protein synthesis inhibitor anisomycin. We have found that the activation kinetics of p38α SAPK in response to these insults is different and also leads to a complex gene pattern response specific for a given stress with a restricted set of overlapping genes. In addition, we have analysed the contribution of p38α the major p38 family member present in MEFs, to the overall stress-induced transcriptional response by using both a chemical inhibitor (SB203580) and p38α deficient (p38α-/-) MEFs. We show here that p38 SAPK dependency ranged between 60% and 88% depending on the treatments and that there is a very good overlap between the inhibitor treatment and the ko cells. Furthermore, we have found that the dependency of SAPK varies depending on the time the cells are subjected to osmostress.ConclusionsOur genome-wide transcriptional analyses shows a selective response to specific stimuli and a restricted common response of up to 20% of the stress up-regulated early genes that involves an important set of transcription factors, which might be critical for either cell adaptation or preparation for continuous extra-cellular changes. Interestingly, up to 85% of the up-regulated genes are under the transcriptional control of p38 SAPK. Thus, activation of p38 SAPK is critical to elicit the early gene expression program required for cell adaptation to stress.
Highlights
Cells have the ability to respond and adapt to environmental changes through activation of stressactivated protein kinases (SAPKs)
It has been shown that p38 MAPK signalling participates in the regulation of gene transcription little is known on the molecular mechanisms used by this SAPK to regulate stress-responsive gene expression as well as the overall set of genes regulated by p38 in response to different stimuli [9]. p38 SAPK transcriptional profiles have been described in primary endothelial cells from human umbilical veins and rat fibroblasts-like synuviocytes after long term incubation with TNFa [10,11], in response to the inhibition of the p38 SAPK in primary human keratinocytes [12] and proliferating cardiomyocites [13]
The activation kinetics of p38a SAPK in response to external insults depends on the stimuli To analyse the kinetics of activation of p38 SAPK in response to several stimuli, we assessed p38 SAPK
Summary
Cells have the ability to respond and adapt to environmental changes through activation of stressactivated protein kinases (SAPKs). P38 SAPK signalling is known to participate in the regulation of gene expression little is known on the molecular mechanisms used by this SAPK to regulate stress-responsive genes and the overall set of genes regulated by p38 in response to different stimuli. Cells have the ability to respond and adapt to environmental changes through the activation of stress-activated protein kinases (SAPKs). It has been shown that p38 MAPK signalling participates in the regulation of gene transcription little is known on the molecular mechanisms used by this SAPK to regulate stress-responsive gene expression as well as the overall set of genes regulated by p38 in response to different stimuli [9]. Comprehensive genome-wide transcription studies describing the involvement of the p38 SAPK on immediate stress-induced genes or a comparative analysis of the genes that respond to different stimuli under the SAPK activation have not been reported to date
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call