title: 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 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.
authors: Department of Molecular, Cellular and Craniofacial Biology, University of Louisville, 501 S. Preston St., Louisville, KY 40202, USA. maia.green@merck.com
authors: M L
authors: ML
authors: Green
authors: A V
authors: AV
authors: Singh
authors: L B
authors: LB
authors: Ruest
authors: M M
authors: MM
authors: Pisano
authors: R A
authors: RA
authors: Prough
authors: T B
authors: TB
authors: Knudsen
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism*; D053263:Gene Regulatory Networks; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000096:biosynthesis / Q000502:physiology; D041681:NIH 3T3 Cells; D012333:RNA, Messenger / Q000096:biosynthesis / Q000502:physiology; D012402:Rotenone; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D012402:Rotenone