Differential programming of p53-deficient embryonic cells during rotenone block

Abstract Mitochondrial dysfunction has been implicated in chemical toxicities. The present study used an in vitro model to investigate the differential expression of metabolic pathways during cellular stress in p53-efficient embryonic fibroblasts compared to p53-deficient cells. These cell lines dif...

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Bibliographic Details
Published in:Toxicology (Amsterdam) 2011-11, Vol.290 (1), p.31-41
Main Authors: Green, M.L, Singh, A.V, Ruest, L.B, Pisano, M.M, Prough, R.A, Knudsen, T.B
Format: Article
Language:English
Subjects:
Animals
biochemical pathways
Biological and medical sciences
Cell Survival - genetics
Cytoskeleton
Embryo
Embryo, Mammalian - cytology
Embryo, Mammalian - metabolism
Emergency
energy
fibroblasts
gene expression
gene expression regulation
Gene Regulatory Networks
genes
Medical sciences
MEF
messenger RNA
Mice
Mice, Knockout
microRNA
MicroRNAs - biosynthesis
MicroRNAs - physiology
miRNA
Mitochondria
Mouse
NAD (coenzyme)
NIH 3T3 Cells
p53
RNA, Messenger - biosynthesis
RNA, Messenger - physiology
Rotenone
Toxicology
tubulin
Tumor Suppressor Protein p53 - deficiency
Tumor Suppressor Protein p53 - genetics
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Summary:Abstract Mitochondrial dysfunction has been implicated in chemical toxicities. The present study used an in vitro model to investigate the differential expression of metabolic pathways during cellular stress in p53-efficient embryonic fibroblasts compared to p53-deficient cells. These cell lines differed with respect to NADH/NAD+ balance. This ratio constitutes a driving force for NAD- and NADH-dependent reactions and is inversed upon exposure to Rotenone (complex I inhibitor). Rotenone perturbed the structure of the elongated fibrillar tubulin network and decreased mRNA expression of tubulin genes both suggesting reprogramming and reorganization of the cytoskeleton in both cell lines. These changes were reflected in the abundance of specific mRNA and microRNA (miRNA) species as determined from genome-based analysis. Changes in mRNA and miRNA expression profiles reflected differences in energy utilizing pathways, consistent with the notion that the p53 pathway influences the cellular response to mitochondrial dysfunction and that at least some control may be embedded within specific mRNA/miRNA networks in embryonic cells.
ISSN:0300-483X
1879-3185
DOI:10.1016/j.tox.2011.08.013