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Analysis of Signalling Pathways Triggering Transcriptional Changes in Adrenal Medulla with Single and Repeated Stress
Author(s) -
Tillinger Andrej,
Liu Xiaoping,
Papanikolaou Nickolaos A,
Serova Lidia I,
Sabban Esther L
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.626.5
Subject(s) - egr1 , microarray analysis techniques , signal transduction , microarray , mapk/erk pathway , biology , hedgehog signaling pathway , kinase , gene expression , microbiology and biotechnology , blot , gene , genetics
The "fight or flight" response of the adrenal medulla (AM) is crucial to restoring homeostasis with acute stress. However, when prolonged or repeated, stress is a major contributor to disease. Here, we examined the changes in gene expression in rat AM with immobilization stress for 2 hr once (IxIMO) or 6 consecutive days (6x IMO). Microarray data from RAE 230 2.0 (Affymetrix), were analyzed by GeneSifter (VizXLabs), and GeneSpringGX (Agilent), and selective genes confirmed by RT‐PCR and western blots. We concentrated on changes in signalling pathways leading to transcriptional responses. Gene Ontology of transcripts significantly (p<0.01) changed showed 248 related to transcription and 315 to signal transduction. The analysis suggested central roles for Fos and Egr1 with single IMO. As Egr family members were induced by both 1x and 6x IMO, Gene Set Enrichment (GSEA) was used to identify pathways and the genes within them enriched with respect to Egr1 expression status and indicated the importance of JAK/STAT and MAP kinase pathways. Panorama Antibody Microarray found different activation of MAPKs by single and repeated IMO, with increased protein levels of ERK 1/2, ERK 5 and p38 with 1xIMO, but not 6xIMO. Several phosphatases were down regulated, especially with single IMO. The results reveal a transition in cell signalling in the AM with repeated exposure to stress. Supported by NIH NS28869.