Naslov
Proteomics-based in silico model of the acute stress threshold

Autori
Fenrich, Matija

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
University of California, Irvine, School of Medicine & J. J. Strossmayer University of Osijek, Faculty of Medicine - Summer School on Stress 2016 / Balog, Marta - Osijek : International Union of Basic & Clinical Pharmacology ; Selye International Institute for advanced studies, 2016, 52-52

Skup
University of California Irvine, School of Medicine & Strossmayer University of Osijek, Faculty of Medicine: Summer School on Stress 2016

Mjesto i datum
Osijek, Hrvatska, 13.06.2016. - 17.06.2016

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Proteomics; Stress; Interactome; Modeling

Sažetak
Stress is a primitive and nonspecific bodily reaction to polimodal stimulaton. A unimodal stimulus alone cannot trigger the stress response, but few stimuli of different modality applied together should regularily result in stress activation. During the metazoan evolution, multicellular organisms have developed the ectoderm, an outermost cellular layer through which the interaction with the environment is carried out, and even its later evolutional derivatives have maintained exactly the same function. Stress is also ectodermally-based and represents a form of interaction with the environment that is highly conserved among species. For that reason, we hypothesize that signaling pathways, activated by polimodal stimulation, share the same highly conserved proteins that are conditioning the threshold for stress reaction in various species. Identification of common nodes in cross-talk between stress-implicated signaling molecules could give us insight about mechanisms underlying the stress threshold on the cellular level. In order to test our hypothesis, we built the signaling pathways networks of ectodermal tissue in C. elegans, Drosophila melanogaster, Mus musculus and Homo sapiens, using the Cytoscape, a software for biomolecular interaction networks analysis. Proteomics data was obtained from the Cytoscape Public Database, Protein Atlas and Human Proteome Map. We corrected the data for homologous proteins, in order to reduce the networks' redundancy. Network analysis revealed edge convergence towards a group of nodes implicated in Mitogene-Activated Kinase (MAPK) signaling in cases where many pathways were activated at the same time. This convergence was non evident when each pathway was active alone, suggesting the polistimulation dependence. The most interacting proteins, regardless of the species, under such conditios were MEKK, ASK, MLK and TAK (corrected for homology). Preliminary results might suggest that under conditions of hyper- and polistimulation, cellular signaling becomes less specifically directed and MAPK pathways are being amplified. Since MAPK signaling mediates DNA-repair, apoptosis, heat schock protein upregulation, cell cycle arrest etc., all of which may be useful in stress, it could be suggested that MAPK amplification may represent a cellular hallmark of the stress threshold trespasing. However, no definite conclusions are to be drawn, because results of in silico experiments are yet to be confirmed or rejected in vivo.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti, Biotehnologija

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