A proteomic analysis of prenatal transfer of microcystin-LR induced neurotoxicity in rat offspring

Recent studies showed that microcystins (MCs) can be transferred to offspring from their adults and exert notable neurotoxicity, but the exact mechanism is little known. In order to better understand cellular responses in brain tissues disrupted by prenatal transfer of MCs, this work mainly focuses on brain impairments of rat offspring. Pregnant SD rats were infused exposed to microcystin-LR (MCLR) at 10 mu g/kg body weight (BW)/day or saline solution from gestational day 8 (GD8) to postnatal day 15 (PD15) of lactation. MCLR accumulation, the levels of malondialdehyde (MDA) and acetylcholine esterase (AChE) activity were detected. The results showed that MCLR enhanced toxin accumulation and MDA, but decreased GSH and the level of AChE activity in the brains of rat offspring. MCLR also caused changes to cerebrum ultrastructure, showing a sparse structure, distention of endoplasmic reticulum and swelling mitochondria. To explore the exact mechanisms, we used a proteomic analysis to identify global brain protein profiles. The proteomic results revealed that MCLR remarkably altered the abundance of 49 proteins that were involved in neurodevelopment, oxidative phosphorylation, cytoskeleton, metabolism, protein folding and degradation. Our results indicated that MCLR exerts neurotoxicity mainly by generating oxidative stress and endoplasmic reliculum stress

The role of apoptosis in MCLR-induced developmental toxicity in zebrafish embryos

We previously demonstrated that cyanobacteria-derived microcystin-leucine-arginine (MCLR) is able to induce developing toxicity, such as malformation, growth delay and also decreased heart rates in zebrafish embryos. However, the molecular mechanisms by which MCLR induces its toxicity during the development of zebrafish remain largely unknown. Here, we evaluate the role of apoptosis in MCLRinduced developmental toxicity. Zebrafish embryos were exposed to various concentrations of MCLR (0, 0.2, 0.5, 2, and 5.0 mg L-1) for 96 h, at which time reactive oxygen species (ROS) was significantly induced in the 2 and 5.0 mg L-1 MCLR exposure groups. Acridine orange (AO) staining and terminal deoxynucleotide transferase-mediated deoxy-UTP nick end labelling (TUNEL) assay showed that MCLR exposure resulted in cell apoptosis. To test the apoptotic pathway, the expression pattern of several apoptoticrelated genes was examined for the level of enzyme activity, gene and protein expression, respectively. The overall results demonstrate that MCLR induced ROS which consequently triggered apoptosis in the heart of developing zebrafish embryos. Our results also indicate that the p53-Bax-Bc1-2 pathway and the caspase-dependent apoptotic pathway play major roles in MCLR-induced apoptosis in the developing embryos. (C) 2014 Elsevier B.V. All rights reserved.We previously demonstrated that cyanobacteria-derived microcystin-leucine-arginine (MCLR) is able to induce developing toxicity, such as malformation, growth delay and also decreased heart rates in zebrafish embryos. However, the molecular mechanisms by which MCLR induces its toxicity during the development of zebrafish remain largely unknown. Here, we evaluate the role of apoptosis in MCLRinduced developmental toxicity. Zebrafish embryos were exposed to various concentrations of MCLR (0, 0.2, 0.5, 2, and 5.0 mg L-1) for 96 h, at which time reactive oxygen species (ROS) was significantly induced in the 2 and 5.0 mg L-1 MCLR exposure groups. Acridine orange (AO) staining and terminal deoxynucleotide transferase-mediated deoxy-UTP nick end labelling (TUNEL) assay showed that MCLR exposure resulted in cell apoptosis. To test the apoptotic pathway, the expression pattern of several apoptoticrelated genes was examined for the level of enzyme activity, gene and protein expression, respectively. The overall results demonstrate that MCLR induced ROS which consequently triggered apoptosis in the heart of developing zebrafish embryos. Our results also indicate that the p53-Bax-Bc1-2 pathway and the caspase-dependent apoptotic pathway play major roles in MCLR-induced apoptosis in the developing embryos. (C) 2014 Elsevier B.V. All rights reserved