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Sci Rep
2016 Aug 26;6:32157. doi: 10.1038/srep32157.
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New insights into negative effects of lithium on sea urchin Paracentrotus lividus embryos.
Ruocco N
,
Costantini M
,
Santella L
.
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The diffuse use of lithium in a number of industrial processes has produced a significant contamination of groundwater and surface water with it. The increased use of lithium has generated only scarce studies on its concentrations in ambient waters and on its effects on aquatic organisms. Only few contributions have focused on the toxicity of lithium in marine organisms (such as marine animals, algae and vegetables), showing that the toxic effect depends on the animal species. In the present study we describe the morphological and the molecular effects of lithium chloride (LiCl), using the sea urchin Paracentrotus lividus as a model organism. We show that LiCl, if added to the eggs before fertilization, induces malformations in the embryos in a dose-dependent manner. We have also followed by RT qPCR the expression levels of thirty seven genes (belonging to different classes of functional processes, such as stress, development, differentiation, skeletogenesis and detoxifications) to identify the molecular targets of LiCl. This study opens new perspectives for the understanding of the mechanism of action of lithium on marine organisms. The findings may also have relevance outside the world of marine organisms since lithium is widely prescribed for the treatment of human bipolar disorders.
Figure 1. Malformations induced by LiCl.Examples of malformations induced in (BâE) Paracentrotus lividus plutei treated with LiCl from 1.0 to 10âmM and observed at 48âhpf in comparison with (A) embryos in sea water without LiCl. Photos were taken with a Zeiss Axiovert 135TV, 10x/0.30, magnification / numerical aperture. Bar, 50âμM.
Figure 2. Percentage of abnormal plutei.Percentage of abnormal plutei (at 48âhpf) in P. lividus eggs incubated with LiCl 10âminutes before fertilization and then fertilized (A) and in eggs treated with LiCl 10âminutes after fertilization (B). Different concentrations of LiCl were used: 1, 2, 3, 4, 5 and 10âmM. Significant differences compared to the control (4.3â±â0.8 abnormal embryos): ***pâ<â0.001 (Studentâs t-test, GraphPad Software Inc., San Diego, CA, USA). Experiments were conducted in triplicate using three egg groups collected from three different females.
Figure 3. Malformations in sea urchin embryos at one week after fertilization.Examples of malformed embryos induced in P. lividus embryos at one week of incubation with LiCl 5 and 10âmM (BâL), in comparison with control embryos in sea water without LiCl (A). Photos were taken with a Zeiss Axiovert 135TV, 10x/0.30 (magnification/numerical aperture). Bar, 50 μM.
Figure 5. Experiments with LiCl 80âmM.Embryos observed at 21âhpf (B) and 48âhpf (C), when eggs were incubated with LiCl 80âmM and then fertilized; (A) shows control embryos (embryos in sea water without LiCl) at 21âhpf.
Figure 7. Gene expression by Real Time qPCR.Histograms showing the differences in expression levels of the genes analysed by Real Time qPCR. P. lividus embryos were grown in the presence of LiCl and collected at different developmental stages: early blastula (5âhpf), late gastrula (21âhpf) and pluteus (48âhpf). Data are reported as a fold difference compared to control embryos in sea water without HEPES (meanâ±âSD). Fold differences greater thanâ±1 (see dotted horizontal guidelines at values of 1 and â1) were considered significant.
Adityanjee,
The syndrome of irreversible lithium-effectuated neurotoxicity.
2005, Pubmed
Adityanjee,
The syndrome of irreversible lithium-effectuated neurotoxicity.
2005,
Pubmed
Ali,
Teratological effects of a panel of sixty water-soluble toxicants on zebrafish development.
2014,
Pubmed
Allagui,
Lithium toxicity and expression of stress-related genes or proteins in A549 cells.
2007,
Pubmed
Aluigi,
The sea urchin, Paracentrotus lividus, embryo as a "bioethical" model for neurodevelopmental toxicity testing: effects of diazinon on the intracellular distribution of OTX2-like proteins.
2008,
Pubmed
,
Echinobase
ANDERSON,
The toxicity thresholds of various sodium salts determined by the use of Daphnia magna.
1946,
Pubmed
Aral,
Toxicity of lithium to humans and the environment--a literature review.
2008,
Pubmed
Becchetti,
Lithium blocks cell cycle transitions in the first cell cycles of sea urchin embryos, an effect rescued by myo-inositol.
1997,
Pubmed
,
Echinobase
Ben-Tabou de-Leon,
Gene regulatory control in the sea urchin aboral ectoderm: spatial initiation, signaling inputs, and cell fate lockdown.
2013,
Pubmed
,
Echinobase
Berridge,
Neural and developmental actions of lithium: a unifying hypothesis.
1989,
Pubmed
Berridge,
Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glands.
1982,
Pubmed
Berridge,
The Albert Lasker Medical Awards. Inositol trisphosphate, calcium, lithium, and cell signaling.
1989,
Pubmed
Berridge,
Unlocking the secrets of cell signaling.
2005,
Pubmed
Bocchetta,
Thyroid abnormalities during lithium treatment.
1991,
Pubmed
Bonaventura,
UVB radiation prevents skeleton growth and stimulates the expression of stress markers in sea urchin embryos.
2005,
Pubmed
,
Echinobase
Bonaventura,
Stress response gene activation protects sea urchin embryos exposed to X-rays.
2011,
Pubmed
,
Echinobase
Busa,
Lithium-induced teratogenesis in frog embryos prevented by a polyphosphoinositide cycle intermediate or a diacylglycerol analog.
1989,
Pubmed
Byrne,
Global change ecotoxicology: Identification of early life history bottlenecks in marine invertebrates, variable species responses and variable experimental approaches.
2012,
Pubmed
Cai,
Overexpressed glutamine synthetase gene modifies nitrogen metabolism and abiotic stress responses in rice.
2009,
Pubmed
Chalecka-Franaszek,
Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons.
1999,
Pubmed
Chen,
Lithium inhibits ceramide- and etoposide-induced protein phosphatase 2A methylation, Bcl-2 dephosphorylation, caspase-2 activation, and apoptosis.
2006,
Pubmed
Chun,
Early events of fertilization in sea urchin eggs are sensitive to actin-binding organic molecules.
2014,
Pubmed
,
Echinobase
Chun,
The biphasic increase of PIP2 in the fertilized eggs of starfish: new roles in actin polymerization and Ca2+ signaling.
2010,
Pubmed
,
Echinobase
Ciapa,
Two phases of inositol polyphosphate and diacylglycerol production at fertilisation.
1986,
Pubmed
,
Echinobase
Ciapa,
Effect of lithium on ionic balance and polyphosphoinositide metabolism during larval vegetalization of the sea urchin Paracentrotus lividus.
1993,
Pubmed
,
Echinobase
Clarke,
p53, mutation frequency and apoptosis in the murine small intestine.
1997,
Pubmed
Costa,
Phylogenetic analysis and expression patterns of p16 and p19 in Paracentrotus lividus embryos.
2012,
Pubmed
,
Echinobase
Crawford,
Lithium chloride inhibits development along the animal vegetal axis and anterior midline of the squid embryo.
2003,
Pubmed
de Nadal,
Controlling gene expression in response to stress.
2011,
Pubmed
Drummond,
The interaction of lithium with thyrotropin-releasing hormone-stimulated lipid metabolism in GH3 pituitary tumour cells. Enhancement of stimulated 1,2-diacylglycerol formation.
1984,
Pubmed
Duboc,
Left-right asymmetry in the sea urchin embryo is regulated by nodal signaling on the right side.
2005,
Pubmed
,
Echinobase
Efrati,
N-Acetylcysteine ameliorates lithium-induced renal failure in rats.
2005,
Pubmed
Falugi,
Toxicity of metal oxide nanoparticles in immune cells of the sea urchin.
2012,
Pubmed
,
Echinobase
Fredieu,
Xwnt-8 and lithium can act upon either dorsal mesodermal or neurectodermal cells to cause a loss of forebrain in Xenopus embryos.
1997,
Pubmed
Geddes,
Long-term lithium therapy for bipolar disorder: systematic review and meta-analysis of randomized controlled trials.
2004,
Pubmed
Gelenberg,
Comparison of standard and low serum levels of lithium for maintenance treatment of bipolar disorder.
1989,
Pubmed
Graeber,
Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours.
1996,
Pubmed
Greenspan,
Inhalation toxicity of lithium combustion aerosols in rats.
1986,
Pubmed
Halet,
The dynamics of plasma membrane PtdIns(4,5)P(2) at fertilization of mouse eggs.
2002,
Pubmed
Hamilton,
Hazard assessment of inorganics to three endangered fish in the Green River, Utah.
1995,
Pubmed
Hill,
Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development.
2013,
Pubmed
Israely,
Deletion of the neuron-specific protein delta-catenin leads to severe cognitive and synaptic dysfunction.
2004,
Pubmed
Kiełczykowska,
The effect of lithium administration in a diet on the chosen parameters of the antioxidant barrier in rats.
2004,
Pubmed
Klein,
A molecular mechanism for the effect of lithium on development.
1996,
Pubmed
Kremer,
GSK3 and Alzheimer's Disease: Facts and Fiction….
2011,
Pubmed
Kszos,
Review of lithium in the aquatic environment: distribution in the United States, toxicity and case example of groundwater contamination.
2003,
Pubmed
Lai,
Cytoprotection by lithium and valproate varies between cell types and cellular stresses.
2006,
Pubmed
Lazarus,
The effects of lithium therapy on thyroid and thyrotropin-releasing hormone.
1998,
Pubmed
Lee,
Overexpression of the glutamine synthetase gene modulates oxidative stress response in rice after exposure to cadmium stress.
2013,
Pubmed
Lepage,
Spatial expression of the hatching enzyme gene in the sea urchin embryo.
1992,
Pubmed
,
Echinobase
Leroy,
Effects of lithium chloride and retinoic acid on the expression of genes from the Xenopus laevis Hox 2 complex.
1992,
Pubmed
Lesser,
Exposure to ultraviolet radiation causes apoptosis in developing sea urchin embryos.
2003,
Pubmed
,
Echinobase
Lister,
Sea ice protects the embryos of the Antarctic sea urchin Sterechinus neumayeri from oxidative damage due to naturally enhanced levels of UV-B radiation.
2010,
Pubmed
,
Echinobase
Livingston,
Lithium evokes expression of vegetal-specific molecules in the animal blastomeres of sea urchin embryos.
1989,
Pubmed
,
Echinobase
Livingston,
Phorbol esters alter cell fate during development of sea urchin embryos.
1992,
Pubmed
,
Echinobase
Long,
Lithium chloride: a flow-through embryo-larval toxicity test with the fathead minnow, Pimephales promelas Rafinesque.
1998,
Pubmed
Maeda,
Influence of ionic conditions on cell differentiation and morphogenesis of the cellular slime molds.
1970,
Pubmed
Marrone,
Defensome against toxic diatom aldehydes in the sea urchin Paracentrotus lividus.
2012,
Pubmed
,
Echinobase
Maslanski,
Lithium-sensitive production of inositol phosphates during amphibian embryonic mesoderm induction.
1992,
Pubmed
Migliaccio,
Stress response to cadmium and manganese in Paracentrotus lividus developing embryos is mediated by nitric oxide.
2014,
Pubmed
,
Echinobase
Nocente-McGrath,
Altered cell fate in LiCl-treated sea urchin embryos.
1991,
Pubmed
,
Echinobase
O'Brien,
Validating GSK3 as an in vivo target of lithium action.
2009,
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,
Sea urchin embryos as an in vivo model for the assessment of manganese toxicity: developmental and stress response effects.
2010,
Pubmed
,
Echinobase
Renzing,
Oxidative stress is involved in the UV activation of p53.
1996,
Pubmed
Ruocco,
Diatom-derived oxylipins induce cell death in sea urchin embryos activating caspase-8 and caspase 3/7.
2016,
Pubmed
,
Echinobase
Russo,
Stress to cadmium monitored by metallothionein gene induction in Paracentrotus lividus embryos.
2003,
Pubmed
,
Echinobase
Santella,
Fertilization in echinoderms.
2012,
Pubmed
,
Echinobase
Santella,
Calcium and fertilization: the beginning of life.
2004,
Pubmed
Santella,
Calcium and actin in the saga of awakening oocytes.
2015,
Pubmed
,
Echinobase
Schou,
Lithium treatment at 52.
2001,
Pubmed
Schrauzer,
Lithium: occurrence, dietary intakes, nutritional essentiality.
2002,
Pubmed
Sconzo,
Effect of the IMPase inhibitor L690,330 on sea urchin development.
1998,
Pubmed
,
Echinobase
Shaldubina,
The mechanism of lithium action: state of the art, ten years later.
2001,
Pubmed
Shao,
Chronic treatment with mood stabilizers lithium and valproate prevents excitotoxicity by inhibiting oxidative stress in rat cerebral cortical cells.
2005,
Pubmed
Stachel,
Lithium perturbation and goosecoid expression identify a dorsal specification pathway in the pregastrula zebrafish.
1993,
Pubmed
Tam,
Nephrotic syndrome and renal insufficiency associated with lithium therapy.
1996,
Pubmed
Teixeira,
Salt stress affects glutamine synthetase activity and mRNA accumulation on potato plants in an organ-dependent manner.
2009,
Pubmed
Teo,
Specific inhibition of CBP/beta-catenin interaction rescues defects in neuronal differentiation caused by a presenilin-1 mutation.
2005,
Pubmed
Thiels,
Pharmacotherapy of psychiatric disorder in pregnancy and during breastfeeding: a review.
1987,
Pubmed
Turan,
Effects of short- and long-term lithium treatment on kidney functioning in patients with bipolar mood disorder.
2002,
Pubmed
Turner,
Fertilization increases the polyphosphoinositide content of sea urchin eggs.
1984,
Pubmed
,
Echinobase
Van Lookeren Campagne,
Lithium respecifies cyclic AMP-induced cell-type specific gene expression in Dictyostelium.
1988,
Pubmed
van Uden,
Regulation of hypoxia-inducible factor-1alpha by NF-kappaB.
2008,
Pubmed
Varrella,
Molecular response to toxic diatom-derived aldehydes in the sea urchin Paracentrotus lividus.
2014,
Pubmed
,
Echinobase
Varrella,
Toxic Diatom Aldehydes Affect Defence Gene Networks in Sea Urchins.
2016,
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
Vasilev,
Effects of ionomycin on egg activation and early development in starfish.
2012,
Pubmed
,
Echinobase
Williams,
A molecular cell biology of lithium.
2004,
Pubmed
Wu,
GSK3: a multifaceted kinase in Wnt signaling.
2010,
Pubmed
Yazaki,
Ca²⁺ influx-linked protein kinase C activity regulates the β-catenin localization, micromere induction signalling and the oral-aboral axis formation in early sea urchin embryos.
2015,
Pubmed
,
Echinobase