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PLoS One
2016 Jan 01;112:e0149734. doi: 10.1371/journal.pone.0149734.
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Toxic Diatom Aldehydes Affect Defence Gene Networks in Sea Urchins.
Varrella S, Romano G, Costantini S, Ruocco N, Ianora A, Bentley MG, Costantini M.
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Marine organisms possess a series of cellular strategies to counteract the negative effects of toxic compounds, including the massive reorganization of gene expression networks. Here we report the modulated dose-dependent response of activated genes by diatom polyunsaturated aldehydes (PUAs) in the sea urchin Paracentrotus lividus. PUAs are secondary metabolites deriving from the oxidation of fatty acids, inducing deleterious effects on the reproduction and development of planktonic and benthic organisms that feed on these unicellular algae and with anti-cancer activity. Our previous results showed that PUAs target several genes, implicated in different functional processes in this sea urchin. Using interactomic Ingenuity Pathway Analysis we now show that the genes targeted by PUAs are correlated with four HUB genes, NF-κB, p53, δ-2-catenin and HIF1A, which have not been previously reported for P. lividus. We propose a working model describing hypothetical pathways potentially involved in toxic aldehyde stress response in sea urchins. This represents the first report on gene networks affected by PUAs, opening new perspectives in understanding the cellular mechanisms underlying the response of benthic organisms to diatom exposure.
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Fig 1. Gene functional classes.The scheme indicates the four functional classes of genes used to which the thirty one genes analyzed in the present study belong: canonical stress genes, genes involved in detoxification processes, genes involved in developmental and differentiation processes and skeletogenic genes.
Fig 2. Dose-dependent variation of gene expression levels induced by decadienal for the genes analyzed.Histograms show dose-dependent variations in expression levels of decadienal modulated genes. Samples incubated with increasing decadienal concentrations (1.0, 1.3, 1.6, 2.0, 2.3 μM) were collected at different stages of development: early blastula (5hp), swimming blastula (9hpf), prism (24hpf) and pluteus (48 hpf) Data are reported as a fold difference (mean ± SD), compared to the control embryos in sea water without decadienal. Fold differences greater than ±2 (see the dotted horizontal guide lines at the values of +2 and −2) were considered significant. A colour code has been used in the histograms to distinguish the four functional classes of genes: green for stress genes, grey for genes involved in detoxification processes, blue for genes involved in developmental and differentiation processes, and red for skeletogenic genes.
Fig 3. Dose-dependent variation of gene expression levels induced by heptadienal for the genes analyzed.Histograms show dose-dependent variations in expression levels of heptadienal modulated genes. Samples incubated with increasing heptadienal concentrations (2.0, 2.5, 3.0, 5.5, 6.0 μM) were collected at different stages of development: early blastula (5hp), swimming blastula (9hpf), prism (24hpf) and pluteus (48 hpf). For further details see also legend to Fig 2.
Fig 4. Dose-dependent variation of gene expression levels induced by octadienal for the genes analyzed.Histograms show dose-dependent variations in expression levels of octadienal modulated genes. Samples incubated with increasing octadienal concentrations (2.5, 4.0, 4.5, 5.0, 7.0, 8.0 μM) were collected at different stages of development: early blastula (5hp), swimming blastula (9hpf), prism (24hpf) and pluteus (48 hpf). For further details see also legend to Fig 2.
Fig 5. Synopsis of dose-dependent gene expression of genes analyzed.Patterns of dose-dependent up- (red arrows) and down-regulation (blue arrows) of the four classes of genes in the sea urchin, P. lividus, in the presence of the PUAs decadienal, heptadienal and octadienal. Genes with two arrows are up- and down-regulated at different concentrations. The arrows correspond to fold differences greater than ±2, considered significant levels of down- or up-regulation.
Fig 6. Interactomic analysis by Ingenuity Pathway Analysis (IPA) software.The network is displayed graphically as nodes (genes) and edges (the biological relationships between nodes). HUB nodes, genes that share the largest numbers of connections with other genes, are indicated by symbols of different colors: RELA in green; CTNNB1 in red, HIF1A in light blue and TP53 in yellow. The biological relationships between HUB nodes and the other significant genes are indicated by coloured arrows (indicating that a molecule modulates the expression of another), according to the colours of the HUB to which they are connected. The connections between CTNNB1-HIF1A, CTNNB1-RELA are indicated by edges and not by arrowheads because the solid edges indicate direct relationships between molecules due to real chemical modifications and, hence, to formation of direct physical contacts. Interaction between HUB nodes are indicated with grey arrows. Genes associated with HUB genes are reported with grey symbols. For further details on IPA analysis see also Materials and Methods section.
Fig 7. Gene expression level of HUB genes.The histograms show the differences in the expression levels of the four HUB genes followed by real-time qPCR, identified in P. lividus: NF-κB, δ-2-catenin, HIF1A and p53. Embryos were grown in the presence of decadienal, heptadienal and octadienal at teratogenic concentrations (1.6, 3.0 and 4.5 μM, respectively) and collected at different times of development (5, 9, 24 and 48hpf). Data are reported as a fold difference (mean ± SD), compared to the control, embryos in sea water without aldehydes. Fold differences greater than ±2 (see the dotted horizontal guide lines at the values of +2 and −2) were considered significant.
Fig 8. Working model of hypothetical pathways potentially involved in the toxic PUAs stress response.PUAs may be able to activate four HUB genes (δ-2-catenin regulates NF-κB, which regulates HIF1A, which in its turn is regulated by p53; a crosstalk between p53 and NF-κB has been reported in ref. 41) or several genes (belonging to different functional responses). All these genes may induce teratogenesis and/or to apoptosis in the sea urchin embryo.
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