Galasso C et al. (2020), Diatom-Derived Polyunsaturated Aldehydes Activa...

ECB-ART-49720

Int J Mol Sci 2020 Jul 22;2115:. doi: 10.3390/ijms21155201.

Show Gene links Show Anatomy links

Diatom-Derived Polyunsaturated Aldehydes Activate Similar Cell Death Genes in Two Different Systems: Sea Urchin Embryos and Human Cells.

Galasso C , Celentano S , Costantini M , D'Aniello S , Ianora A , Sansone C , Romano G .

???displayArticle.abstract???
Programmed cell death, such as apoptosis and autophagy, are key processes that are activated early on during development, leading to remodelling in embryos and homeostasis in adult organisms. Genomic conservation of death factors has been largely investigated in the animal and plant kingdoms. In this study, we analysed, for the first time, the expression profile of 11 genes involved in apoptosis (extrinsic and intrinsic pathways) and autophagy in sea urchin Paracentrotus lividus embryos exposed to antiproliferative polyunsaturated aldehydes (PUAs), and we compared these results with those obtained on the human cell line A549 treated with the same molecules. We found that sea urchins and human cells activated, at the gene level, a similar cell death response to these compounds. Despite the evolutionary distance between sea urchins and humans, we observed that the activation of apoptotic and autophagic genes in response to cytotoxic compounds is a conserved process. These results give first insight on death mechanisms of P. lividus death mechanisms, also providing additional information for the use of this marine organism as a useful in vitro model for the study of cell death signalling pathways activated in response to chemical compounds.

???displayArticle.pubmedLink??? 32708040
???displayArticle.pmcLink??? PMC7439121
???displayArticle.link??? Int J Mol Sci

???attribute.lit??? ???displayArticles.show???

	Figure 1. Gene expression levels of 11 genes belonging to extrinsic apoptosis (A–D), intrinsic apoptosis (E–H), and autophagy (I–L) in the sea urchin Paracentrotus lividus treated with 1.0, 1.3, 1.6, 2.0, and 2.3 μM of decadienal for 5, 21, and 48 hpf and in A549 human cells treated with 5 μM for 2 h. Samples obtained from three independent biological replicates were analysed by qPCR in technical triplicates. Data are reported as fold difference (mean ± SD), compared to controls without decadienal. Error bars represent the variation in biological replicates. Expression values were statistically analysed by Mann–Whitney U test, and values were considered significant if the p-value was ≤0.05 (* for p-value ≤ 0.05; for p-value ≤ 0.01; * for p-value ≤ 0.001).
	Figure 2. Gene expression levels of 11 genes belonging to extrinsic apoptosis (A–D), intrinsic apoptosis (E–H), and autophagy (I–L) in the sea urchin Paracentrotus lividus treated with 2.0, 2.5, 3.0, 5.5, and 6.0 μM of heptadienal for 5, 21, and 48 hpf and in A549 human cells treated with 5.0 μM for 2 h. Samples obtained from three independent biological replicates were analysed by qPCR in technical triplicates. Data are reported as fold difference (mean ± SD), compared to controls without heptadienal. Error bars represent the variation in biological replicates. Expression values were statistically analysed by Mann–Whitney U test and values were considered significant if the p-value was ≤0.05 (* for p-value ≤ 0.05; for p-value ≤ 0.01; * for p-value ≤ 0.001).
	Figure 3. Gene expression levels of 11 genes belonging to extrinsic apoptosis (A–D), intrinsic apoptosis (E–H), and autophagy (I–L) in the sea urchin Paracentrotus lividus treated with 2.5, 4.0, 4.5, 7.0, and 8.0 μM of octadienal for 5, 21, and 48 hpf and in A549 human cells treated with 5.0 μM for 2 h. Samples obtained from three independent biological replicates were analysed by qPCR in technical triplicates. Data are reported as fold difference (mean ± SD), compared to controls without octadienal. Error bars represent the variation in biological replicates. Expression values greater were statistically analysed by Mann–Whitney U test and values were considered significant if the p-value was ≤0.05 (* for p-value ≤ 0.05; for p-value ≤ 0.01; * for p-value ≤ 0.001).
	Figure 4. Schematic representation of death genes activated in the sea urchin Paracentrotus lividus embryos and A549 human cells. All genes studied by qPCR and significantly upregulated or downregulated by PUAs are represented with a specific colour, whereas caspase 3/7 (represented in a grey rectangle) was already investigated in a previous study [23] and was used in this figure only to complete the pathway. Phagophores engulf cytoplasmic components during autophagy that are delivered to lysosomes for degradation. “DD” refers to decadienal, “HD” refers to heptadienal, and “OD” refers to octadienal.

References [+] :

Arvanitis, Apoptosis in C. elegans: lessons for cancer and immunity. 2013, Pubmed

Arvanitis, Apoptosis in C. elegans: lessons for cancer and immunity. 2013, Pubmed
Blankenberg, Multimodality molecular imaging of apoptosis in oncology. 2011, Pubmed
Calabrese, U-shaped dose-responses in biology, toxicology, and public health. 2001, Pubmed
Caldwell, The influence of bioactive oxylipins from marine diatoms on invertebrate reproduction and development. 2009, Pubmed
Chiarelli, Autophagy as a defense strategy against stress: focus on Paracentrotus lividus sea urchin embryos exposed to cadmium. 2016, Pubmed , Echinobase
Costa, Phylogenetic analysis and expression patterns of p16 and p19 in Paracentrotus lividus embryos. 2012, Pubmed , Echinobase
Crawford, Conservation of caspase substrates across metazoans suggests hierarchical importance of signaling pathways over specific targets and cleavage site motifs in apoptosis. 2012, Pubmed
Crighton, DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. 2006, Pubmed
Cózar, Macroecological patterns of the phytoplankton production of polyunsaturated aldehydes. 2018, Pubmed
Eimon, The zebrafish as a model organism for the study of apoptosis. 2010, Pubmed
Eimon, Delineation of the cell-extrinsic apoptosis pathway in the zebrafish. 2006, Pubmed
Elmore, Apoptosis: a review of programmed cell death. 2007, Pubmed
Fontana, LOX-induced lipid peroxidation mechanism responsible for the detrimental effect of marine diatoms on zooplankton grazers. 2007, Pubmed
Fuchs, Programmed cell death in animal development and disease. 2011, Pubmed
Galasso, The Marine Dinoflagellate Alexandrium minutum Activates a Mitophagic Pathway in Human Lung Cancer Cells. 2018, Pubmed
Galasso, Microalgal Derivatives as Potential Nutraceutical and Food Supplements for Human Health: A Focus on Cancer Prevention and Interception. 2019, Pubmed
Galasso, Identification of Cell Death Genes in Sea Urchin Paracentrotus lividus and Their Expression Patterns during Embryonic Development. 2019, Pubmed , Echinobase
Galluzzi, Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. 2018, Pubmed
Gualtieri, Bisphenol A effect on glutathione synthesis and recycling in testicular Sertoli cells. 2011, Pubmed
Ianora, Toxigenic effects of diatoms on grazers, phytoplankton and other microbes: a review. 2010, Pubmed
Ianora, Aldehyde suppression of copepod recruitment in blooms of a ubiquitous planktonic diatom. 2004, Pubmed
Inohara, Genes with homology to mammalian apoptosis regulators identified in zebrafish. 2000, Pubmed
Jacobson, Programmed cell death in animal development. 1997, Pubmed
Kim, Apoptosis-inducing factor (AIF) inhibits protein synthesis by interacting with the eukaryotic translation initiation factor 3 subunit p44 (eIF3g). 2006, Pubmed
Krammer, CD95's deadly mission in the immune system. 2000, Pubmed
Kubli, Mitochondria and mitophagy: the yin and yang of cell death control. 2012, Pubmed
Leite, Antimitotic activity on sea urchin embryonic cells of seven antiparasitic Morita-Baylis-Hillman adducts: a potential new class of anticancer drugs. 2012, Pubmed , Echinobase
Marrone, Defensome against toxic diatom aldehydes in the sea urchin Paracentrotus lividus. 2012, Pubmed , Echinobase
Morton, AIFM1 mutation presenting with fatal encephalomyopathy and mitochondrial disease in an infant. 2017, Pubmed
Moya, Functional conservation of the apoptotic machinery from coral to man: the diverse and complex Bcl-2 and caspase repertoires of Acropora millepora. 2016, Pubmed
Nagata, Autoimmunity and the clearance of dead cells. 2010, Pubmed
Pfaffl, A new mathematical model for relative quantification in real-time RT-PCR. 2001, Pubmed
Pfaffl, Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. 2002, Pubmed
Pinsino, Titanium dioxide nanoparticles stimulate sea urchin immune cell phagocytic activity involving TLR/p38 MAPK-mediated signalling pathway. 2015, Pubmed , Echinobase
Roca-Agujetas, Recent Insights into the Mitochondrial Role in Autophagy and Its Regulation by Oxidative Stress. 2019, Pubmed
Roccheri, Physiological and induced apoptosis in sea urchin larvae undergoing metamorphosis. 2002, Pubmed , Echinobase
Rojansky, Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1. 2016, Pubmed
Romano, A marine diatom-derived aldehyde induces apoptosis in copepod and sea urchin embryos. 2003, Pubmed , Echinobase
Romano, Nitric oxide mediates the stress response induced by diatom aldehydes in the sea urchin Paracentrotus lividus. 2011, Pubmed , Echinobase
Romano, Teratogenic effects of diatom metabolites on sea urchin Paracentrotus lividus embryos. 2010, Pubmed , Echinobase
Ruocco, Diatom-derived oxylipins induce cell death in sea urchin embryos activating caspase-8 and caspase 3/7. 2016, Pubmed , Echinobase
Ruocco, Toxigenic effects of two benthic diatoms upon grazing activity of the sea urchin: morphological, metabolomic and de novo transcriptomic analysis. 2018, Pubmed , Echinobase
Sannino, Pseudoalteromonas haloplanktis TAC125 produces 4-hydroxybenzoic acid that induces pyroptosis in human A459 lung adenocarcinoma cells. 2018, Pubmed
Sansone, The Marine Dinoflagellate Alexandrium andersoni Induces Cell Death in Lung and Colorectal Tumor Cell Lines. 2018, Pubmed
Sansone, Diatom-derived polyunsaturated aldehydes activate cell death in human cancer cell lines but not normal cells. 2014, Pubmed
Schug, Endocrine disrupting chemicals and disease susceptibility. 2011, Pubmed
Sedger, TNF and TNF-receptors: From mediators of cell death and inflammation to therapeutic giants - past, present and future. 2014, Pubmed
Su, Role of the Crosstalk between Autophagy and Apoptosis in Cancer. 2013, Pubmed
Thorburn, Apoptosis and autophagy: regulatory connections between two supposedly different processes. 2008, Pubmed
Torres-Águila, Diatom bloom-derived biotoxins cause aberrant development and gene expression in the appendicularian chordate Oikopleura dioica. 2018, Pubmed
Varrella, Molecular response to toxic diatom-derived aldehydes in the sea urchin Paracentrotus lividus. 2014, Pubmed , Echinobase
Varrella, First Morphological and Molecular Evidence of the Negative Impact of Diatom-Derived Hydroxyacids on the Sea Urchin Paracentrotus lividus. 2016, Pubmed , Echinobase
Varrella, Toxic Diatom Aldehydes Affect Defence Gene Networks in Sea Urchins. 2016, Pubmed , Echinobase
Vernooy, Cell death regulation in Drosophila: conservation of mechanism and unique insights. 2000, Pubmed
Villunger, When cells die II: a comprehensive evaluation of apoptosis and programmed cell death. 2004, Pubmed
Xu, Genetic control of programmed cell death (apoptosis) in Drosophila. 2009, Pubmed
Zhang, A dual role for poly(ADP-ribose) polymerase-1 during caspase-dependent apoptosis. 2012, Pubmed
Zhao, Role of necroptosis in the pathogenesis of solid organ injury. 2015, Pubmed
Zhou, Elimination of paternal mitochondria through the lysosomal degradation pathway in C. elegans. 2011, Pubmed

	Figure 1. Gene expression levels of 11 genes belonging to extrinsic apoptosis (A–D), intrinsic apoptosis (E–H), and autophagy (I–L) in the sea urchin Paracentrotus lividus treated with 1.0, 1.3, 1.6, 2.0, and 2.3 μM of decadienal for 5, 21, and 48 hpf and in A549 human cells treated with 5 μM for 2 h. Samples obtained from three independent biological replicates were analysed by qPCR in technical triplicates. Data are reported as fold difference (mean ± SD), compared to controls without decadienal. Error bars represent the variation in biological replicates. Expression values were statistically analysed by Mann–Whitney U test, and values were considered significant if the p-value was ≤0.05 (* for p-value ≤ 0.05; for p-value ≤ 0.01; * for p-value ≤ 0.001).
	Figure 2. Gene expression levels of 11 genes belonging to extrinsic apoptosis (A–D), intrinsic apoptosis (E–H), and autophagy (I–L) in the sea urchin Paracentrotus lividus treated with 2.0, 2.5, 3.0, 5.5, and 6.0 μM of heptadienal for 5, 21, and 48 hpf and in A549 human cells treated with 5.0 μM for 2 h. Samples obtained from three independent biological replicates were analysed by qPCR in technical triplicates. Data are reported as fold difference (mean ± SD), compared to controls without heptadienal. Error bars represent the variation in biological replicates. Expression values were statistically analysed by Mann–Whitney U test and values were considered significant if the p-value was ≤0.05 (* for p-value ≤ 0.05; for p-value ≤ 0.01; * for p-value ≤ 0.001).
	Figure 3. Gene expression levels of 11 genes belonging to extrinsic apoptosis (A–D), intrinsic apoptosis (E–H), and autophagy (I–L) in the sea urchin Paracentrotus lividus treated with 2.5, 4.0, 4.5, 7.0, and 8.0 μM of octadienal for 5, 21, and 48 hpf and in A549 human cells treated with 5.0 μM for 2 h. Samples obtained from three independent biological replicates were analysed by qPCR in technical triplicates. Data are reported as fold difference (mean ± SD), compared to controls without octadienal. Error bars represent the variation in biological replicates. Expression values greater were statistically analysed by Mann–Whitney U test and values were considered significant if the p-value was ≤0.05 (* for p-value ≤ 0.05; for p-value ≤ 0.01; * for p-value ≤ 0.001).
	Figure 4. Schematic representation of death genes activated in the sea urchin Paracentrotus lividus embryos and A549 human cells. All genes studied by qPCR and significantly upregulated or downregulated by PUAs are represented with a specific colour, whereas caspase 3/7 (represented in a grey rectangle) was already investigated in a previous study [23] and was used in this figure only to complete the pathway. Phagophores engulf cytoplasmic components during autophagy that are delivered to lysosomes for degradation. “DD” refers to decadienal, “HD” refers to heptadienal, and “OD” refers to octadienal.