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.
Presently, a large effort is being made worldwide to increase the sustainability of industrial development, while preserving not only the quality of the environment but also that of animal and human life. In this work, sea urchin early developmental stages were used as a model to test the effects of the organophosphate pesticide (diazinon) on the regulation of gene expression by immunohistochemical localization of the human regulatory protein against the human OTX2. Egg exposure to diazinon did not affect fertilization; however, at concentrations 10(-5)-10(-6) M, it did cause developmental anomalies, among which was the dose-dependent alteration of the intracellular distribution of a regulatory protein that is immunologically related to the human OTX2. The severe anomalies and developmental delay observed after treatment at 10(-5) M concentration are indicators of systemic toxicity, while the results after treatment at 10(-6) M suggest a specific action of the neurotoxic compound. In this second case, exposure to diazinon caused partial delivery of the protein into the nuclei, a defective translocation that particularly affected the blastula and gastrula stages. Therefore, the possibility that neurotoxic agents such as organophosphates may damage embryonic development is taken into account. Specifically, the compounds are known to alter cytoplasmic dynamics, which play a crucial role in regulating the distribution of intracellular structures and molecules, as well as transcription factors. Speculatively, basing our assumptions on Fura2 experiments, we submit the hypothesis that this effect may be due to altered calcium dynamics, which in turn alter cytoskeleton dynamics: the asters, in fact, appear strongly positive to the OTX2 immunoreaction, in both control and exposed samples. Coimmunoprecipitation experiments seem to supply evidence to the hypothesis.
Aluigi
M G
MG
Dipartimento di Biologia Sperimentale, Ambientale ed Applicata, University of Genova, Genoa, Italy.
Angelini
C
C
Corte
G
G
Falugi
C
C
D000818:Animals; D026688:Bioethical Issues; D002118:Calcium / Q000378:metabolism; D003976:Diazinon / Q000633:toxicity*; D055724:Electrophysiological Phenomena / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects*; D004781:Environmental Exposure; D015151:Immunoblotting; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D009420:Nervous System / Q000187:drug effects / Q000196:embryology*; D051857:Otx Transcription Factors / Q000378:metabolism*; D047328:Paracentrotus / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D021381:Protein Transport / Q000187:drug effects; D013997:Time Factors; D018675:Toxicity Tests; D014404:Tubulin / Q000378:metabolism
D051857:Otx Transcription Factors; D014404:Tubulin; D002118:Calcium; D003976:Diazinon