title: Transcriptional and Behavioral Responses of Zebrafish Larvae to Microcystin-LR Exposure.
abstract: Microcystins are cyclic heptapeptides that constitute a diverse group of toxins produced by cyanobacteria. One of the most toxic variants of this family is microcystin-LR (MCLR) which is a potent inhibitor of protein phosphatase 2A (PP2A) and induces cytoskeleton alterations. In this study, zebrafish larvae exposed to 500 μg/L of MCLR for four days exhibited a 40% reduction of PP2A activity compared to the controls, indicating early effects of the toxin. Gene expression profiling of the MCLR-exposed larvae using microarray analysis revealed that keratin 96 (krt96) was the most downregulated gene, consistent with the well-documented effects of MCLR on cytoskeleton structure. In addition, our analysis revealed upregulation in all genes encoding for the enzymes of the retinal visual cycle, includingrpe65a(retinal pigment epithelium-specific protein 65a), which is critical for the larval vision. Quantitative real-time PCR (qPCR) analysis confirmed the microarray data, showing thatrpe65awas significantly upregulated at 50 μg/L and 500 μg/L MCLR in a dose-dependent manner. Consistent with the microarray data, MCLR-treated larvae displayed behavioral alterations such as weakening response to the sudden darkness and hypoactivity in the dark. Our work reveals new molecular targets for MCLR and provides further insights into the molecular mechanisms of MCLR toxicity during early development.
authors.affiliation: Laboratory of Biological Chemistry, Medical School, University of Ioannina, 45110 Ioannina, Greece. elenatzima@gmail.com.|Division of Biomedical Research, Foundation for Research and Technology-Hellas, Institute of Molecular Biology and Biotechnology, 45110 Ιοannina, Greece. elenatzima@gmail.com.
authors.forename: Eleni
authors.initials: E
authors.lastname: Tzima
authors.affiliation: Laboratory of Biological Chemistry, Medical School, University of Ioannina, 45110 Ioannina, Greece. iliana.serifi@gmail.com.|Division of Biomedical Research, Foundation for Research and Technology-Hellas, Institute of Molecular Biology and Biotechnology, 45110 Ιοannina, Greece. iliana.serifi@gmail.com.
authors.forename: Iliana
authors.initials: I
authors.lastname: Serifi
authors.affiliation: Laboratory of Biological Chemistry, Medical School, University of Ioannina, 45110 Ioannina, Greece. juanita_tsiki@hotmail.com.
authors.forename: Ioanna
authors.initials: I
authors.lastname: Tsikari
authors.affiliation: BIOBIDE, Paseo Mikeletegi 56, 20009 San Sebastian, Spain. alzualde@biobide.es.
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Alzualde
authors.affiliation: Laboratory of Zoology, Department of Biological Applications and Technologies, University of Ioannina, 45110 Ioannina, Greece. ileonard@uoi.gr.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Leonardos
authors.affiliation: Laboratory of Biological Chemistry, Medical School, University of Ioannina, 45110 Ioannina, Greece. thpapama@uoi.gr.|Division of Biomedical Research, Foundation for Research and Technology-Hellas, Institute of Molecular Biology and Biotechnology, 45110 Ιοannina, Greece. thpapama@uoi.gr.
authors.forename: Thomais
authors.initials: T
authors.lastname: Papamarcaki
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D007814:Larva / Q000187:drug effects* / Q000235:genetics*; D008387:Marine Toxins; D052998:Microcystins / Q000494:pharmacology*; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D015027:Zebrafish / Q000235:genetics*
chemical_list: D008387:Marine Toxins; D052998:Microcystins; D054648:Protein Phosphatase 2; C057862:cyanoginosin LR
keywords: MCLR; behavior; gene expression; visual cycle; zebrafish