Details:

Alternative Title:
Chem Res Toxicol
Publisher's site:
http://dx.doi.org/10.1021/tx500085u
Personal Author:
Waters, Katrina M. ; Cummings, Brian S. ; Shankaran, Harish ; Scholpa, Natalie E. ; Weber, Thomas J.
Waters, Katrina M. ; Cummings, Brian S. ; Shankaran, Harish ; Scholpa, Natalie E. ; Weber, Thomas J. Less -
Description:
Studies were undertaken to determine whether extracellular signal regulated kinase (ERK) oscillations regulate a unique subset of genes in human keratinocytes and subsequently whether the p38 stress response inhibits ERK oscillations. A DNA microarray identified many genes that were unique to ERK oscillations, and network reconstruction predicted an important role for the mediator complex subunit 1 (MED1) node in mediating ERK oscillation-dependent gene expression. Increased ERK-dependent phosphorylation of MED1 was observed in oscillating cells compared to nonoscillating counterparts as validation. Treatment of keratinocytes with a p38 inhibitor (SB203580) increased ERK oscillation amplitudes and MED1 and phospho-MED1 protein levels. Bromate is a probable human carcinogen that activates p38. Bromate inhibited ERK oscillations in human keratinocytes and JB6 cells and induced an increase in phospho-p38 and a decrease in phospho-MED1 protein levels. Treatment of normal rat kidney cells and primary salivary gland epithelial cells with bromate decreased phospho-MED1 levels in a reversible fashion upon treatment with p38 inhibitors (SB202190; SB203580). Our results indicate that oscillatory behavior in the ERK pathway alters homeostatic gene regulation patterns and that the cellular response to perturbation may manifest differently in oscillating vs nonoscillating cells.
Subject:
[+]
Article
Bromates
Cells, Cultured
Epithelial Cells
Extracellular Signal-Regulated MAP Kinases
Gene Expression Regulation
Humans
Imidazoles
Keratinocytes
Mediator Complex Subunit 1
Oligonucleotide Array Sequence Analysis
P38 Mitogen-Activated Protein Kinases
Phosphorylation
Pyridines

Source:
Chem Res Toxicol. 2014; 27(9):1496-1503.
Pubmed ID:
25068892
Pubmed Central ID:
PMC4163986
Document Type:
Journal Article
Funding:
R01 EB016100/EB/NIBIB NIH HHS/United States ; R01EB0116100/EB/NIBIB NIH HHS/United States ; R01OH008173-06/OH/NIOSH CDC HHS/United States ; R21EB08153/EB/NIBIB NIH HHS/United States
R01 EB016100/EB/NIBIB NIH HHS/United States ; R01EB0116100/EB/NIBIB NIH HHS/United States ; R01OH008173-06/OH/NIOSH CDC HHS/United States ; R21EB08153/EB/NIBIB NIH HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:518325a9e1cb94417eeaa2ec3ed237df5c7693b0b708aef7e79c76169ae78f96
File Type:

Supporting Files

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