Biomedical subjects

Marianne Barrier

Publications and source records attributed to Marianne Barrier.

5 recordsLinked to original sources

PubMed2006

Teratogen-induced activation of p53 in early postimplantation mouse embryos.

Hyperthermia (HS) and 4-hydroperoxycyclophosphamide (4CP) activate the mitochondrial apoptotic pathway in day 9 mouse embryos. Previous microarray analyses Microarray analyses revealed that several p53 target genes are upregulated after exposure to HS or 4CP, suggesting a role for p53 in teratogen-induced apoptosis. To explore the role of p53, we assessed the activation of p53 in day 9 mouse embryos exposed to HS or 4CP in vitro. Both teratogens induced the accumulation of p53 and phosphorylation of p53 at ser-15, two hallmarks of p53 activation. HS and 4CP also induced an increase in Noxa and Puma mRNAs, transcripts of two known proapoptotic p53 target genes; however, these two teratogens did not induce significant increases in NOXA and PUMA proteins, suggesting that p53 does not activate the mitochondrial apoptotic pathway by transcriptionally upregulating the expression of NOXA and PUMA proteins. HS and 4CP also induced the expression of p21 mRNA and protein, suggesting a role for p53 in teratogen-induced cell cycle arrest. Previously, we also showed that HS and 4CP activate the apoptotic pathway in the embryo proper (head and trunk) but not in the heart. We now show that HS and 4CP induce a robust activation of p53 in the embryo proper but an attenuated induction in the heart. HS and 4CP induce the expression of p21 protein in majority of the cells in the embryo; however, expression of NOXA and PUMA proteins were not significantly induced in heads, hearts, or trunks of day 9 embryos. Overall, our results suggest that p53 may play a transcription-dependent role in teratogen-induced cell cycle arrest but a transcription-independent role in teratogen-induced apoptosis in day 9 mouse embryos exposed to HS or 4CP.

Animals↗

PubMed2006

Role of miRNA and miRNA processing factors in development and disease.

Mature microRNAs (miRNAs) are single-stranded RNA molecules of 17-24 nucleotides (nt) in length that are encoded in the genomes of plants and animals. The seminal discoveries of miRNA made in C. elegans have led the way to the rampant discoveries being made today in this field. Since each miRNA is predicted and in some cases confirmed to regulate multiple genes, the potential regulatory circuitry afforded by miRNAs is thought to be enormous and could amount to regulation of >30% of all human genes. Due to the sequences of many of the miRNAs being highly homologous among organisms, the huge potential of miRNAs to regulate gene expression, and the hints of miRNAs being useful in both diagnostics and therapeutics, it is no wonder these small RNAs are gaining such popularity in both the academic and industrial settings. It is now becoming clear that the miRNA gene class represents a very important gene regulatory network. This article reviews the initial discoveries of miRNA that began in the nematode C. elegans, and extends into what is known about miRNAs and miRNA processing factors in mouse development and human disease.

Animals↗

PubMed2004

Alterations in gene expression induced in day-9 mouse embryos exposed to hyperthermia (HS) or 4-hydroperoxycyclophosphamide (4CP): analysis using cDNA microarrays.

Teratogen-induced alterations in gene expression play an important role in the genesis of malformations in animals. The recent development of DNA microarrays now offers the opportunity to monitor global changes in gene expression and therefore the potential to obtain significant new information concerning both normal and abnormal development. RNA was isolated from day-9 mouse embryos at 1 and 5 h after exposure to hyperthermia (HS) or 4-hydroperoxycyclophosphamide (4CP) and compared to RNA isolated from concurrent controls using mouse cDNA microarrays. Cy5/Cy3 intensity data were extracted using Spot-on Image software and then normalized using the statistical software program R/maanova. Differentially expressed genes were identified using a linear mixed-effects model and p values derived from t-test statistics. Approximately 9000 genes show statistically significant alterations in expression in day-9 mouse embryos exposed to HS or 4CP. HS and 4CP also induce alterations in the expression of distinct sets of genes, e.g., DNA replication/repair, cell cycle, signal transduction, and transcription-related genes. As expected, a variety of heat shock genes are upregulated by HS but not 4CP. Among genes whose expression is altered by both HS and 4CP, cluster analysis identified three p53 target genes (Cyclin G1, Gtse1, and Mdm2), and follow up studies confirmed that p53 is activated in embryos exposed to these two teratogens. In addition, cluster analyses also revealed that HS but not 4CP induces the downregulation of genes encoding key enzymes in the cholesterol biosynthesis pathway. Thus, our microarray data have identified one potentially important pathway (p53) common to both HS- and 4CP-induced teratogenesis and another pathway (cholesterol biosynthesis) potentially important, but specific to HS-induced teratogenesis.

Animals↗

PubMed2003

Selection on rapidly evolving proteins in the Arabidopsis genome.

Genes that have undergone positive or diversifying selection are likely to be associated with adaptive divergence between species. One indicator of adaptive selection at the molecular level is an excess of amino acid replacement fixed differences per replacement site relative to the number of synonymous fixed differences per synonymous site (omega = K(a)/K(s)). We used an evolutionary expressed sequence tag (EST) approach to estimate the distribution of omega among 304 orthologous loci between Arabidopsis thaliana and A. lyrata to identify genes potentially involved in the adaptive divergence between these two Brassicaceae species. We find that 14 of 304 genes (approximately 5%) have an estimated omega > 1 and are candidates for genes with increased selection intensities. Molecular population genetic analyses of 6 of these rapidly evolving protein loci indicate that, despite their high levels of between-species nonsynonymous divergence, these genes do not have elevated levels of intraspecific replacement polymorphisms compared to previously studied genes. A hierarchical Bayesian analysis of protein-coding region evolution within and between species also indicates that the selection intensities of these genes are elevated compared to previously studied A. thaliana nuclear loci.

Arabidopsis↗

PubMedDate not supplied

Proteomics in developmental toxicology.

The objective of this presentation is to review the major proteomic technologies available to developmental toxicologists and, when possible, to provide examples of how various proteomic technologies have been used in developmental toxicology or toxicology in general. The field of proteomics is too broad for us to go into great depth about each technology, so we have attempted to provide brief overviews supplemented with many references that cover the subjects in more detail. Proteomics tools produce a global view of complex biological systems by examining complex protein mixtures using large-scale, high-throughput technologies. These technologies speed up the process of protein separation, quantification, and identification. As an important complement to genomics, proteomics allows for the examination of the entire complement of proteins in an organism, tissue, or cell-type. Current proteomics technologies not only identify protein expression, but also post-translational modifications and protein interactions. The field of proteomics is expanding rapidly to provide greater volume and quality of protein information to help understand the multifaceted nature of biological systems.

Animals↗