title: Microcystin-LR activates the ERK1/2 kinases and stimulates the proliferation of the monkey kidney-derived cell line Vero-E6.
abstract: Microcystin-LR (MCLR) is a peptide produced by freshwater cyanobacteria that induces severe hepatotoxicity in humans and animals. MCLR is also a potent tumour promoter and it has been proposed that this activity is mediated by the inhibition of protein phosphatases PP1/PP2A, possibly through the activation of proto-oncogenes c-jun, c-fos and c-myc. However, the mechanisms underlying MCLR-induced tumour promotion are still largely unknown, particularly in non-liver cells. In previous studies we have demonstrated that micromolar concentrations of MCLR induce cytotoxic effects in the kidney Vero-E6 cell line. The purpose of the present work was to evaluate whether the exposure to subcytotoxic concentrations of MCLR was sufficient to induce the proliferation of Vero-E6 cells. Through BrdU incorporation assay we show that at nanomolar concentrations MCLR stimulates cell cycle progression in Vero-E6 kidney cell line. Moreover, the analysis of mitogen-activated protein kinases p38, JNK and ERK1/2 activity revealed that the proliferative effect of MCLR is associated with the activation of the pro-proliferative ERK1/2 pathway. These results emphasise the importance to confirm in vivo the impact of MCLR on tumour promotion at kidney level.
authors.affiliation: National Institute of Health Dr. Ricardo Jorge, Department of Genetics, Lisbon, Portugal. elsa.dias@insa.min-saude.pt
authors.forename: E
authors.initials: E
authors.lastname: Dias
authors.forename: P
authors.initials: P
authors.lastname: Matos
authors.forename: P
authors.initials: P
authors.lastname: Pereira
authors.forename: M C C
authors.initials: MC
authors.lastname: Batoréu
authors.forename: M J
authors.initials: MJ
authors.lastname: Silva
authors.forename: P
authors.initials: P
authors.lastname: Jordan
mesh_terms: D000818:Animals; D001427:Bacterial Toxins / Q000302:isolation & purification / Q000633:toxicity*; D002273:Carcinogens / Q000302:isolation & purification / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000633:toxicity*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis*; D008387:Marine Toxins; D052998:Microcystins / Q000302:isolation & purification / Q000633:toxicity*; D046931:Microcystis / Q000737:chemistry / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000096:biosynthesis; D048052:Mitogen-Activated Protein Kinase 3 / Q000096:biosynthesis; D014709:Vero Cells / Q000187:drug effects* / Q000201:enzymology
chemical_list: D001427:Bacterial Toxins; D002273:Carcinogens; D004791:Enzyme Inhibitors; D008387:Marine Toxins; D052998:Microcystins; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C057862:cyanoginosin LR