Search

Microcystin-LR (MC-LR), a cyclic heptapeptide toxin produced by cyanobacteria, was found to induce genotoxic actions in various types of cells. Some investigators reported that microcystin-LR acted as tumor initiator in the observed genotoxic action mediated by this cyanotoxin. However, the underlying mechanisms underlying MC-induced DNA damage in the human intestine epithelium cell line (NCM460) are not known. The purpose of this study was to examine the influence of 24 hr exposure to 5 or 10 µM MC-LR on intestinal DNA damage using NCM460 intestine cell line as a model. Data showed that MC-LR increased Olive tail moment (OTM) as evidenced by the comet assay, inhibited protein phosphatase 2A (PP2A) activity, elevated reactive oxygen species levels (ROS) and enhanced γ-H2AX and p-p53 protein expression levels. Results indicated that MC-LR produced intestinal DNA damage by inhibiting PP2A activity, activating p53 protein and subsequently initiating excess generation of ROS. These observations suggest that MC-LR–induced intestinal DNA damage involves a complex series of events that include oxidant stress, PP2A enzymic inhibition and activation of p53 protein. [ABSTRACT FROM AUTHOR]

Microcystin-LR (MC-LR), a frequently occurring hepatotoxic cyanotoxin produced by cyanobacterial blooms, poses a great threat to human health. However, the precise molecular mechanisms underlying MC-LR-induced hepatotoxicity remain to be determined. Recent investigators found that in many human diseases circular RNAs (circRNAs) a class of endogenous non-coding RNAs played critical roles in disease outcomes. The aim of this study was to investigate whether circRNAs were involved in MC-LR-mediated hepatotoxicity using human normal liver cell line (HL7702). Using high-throughput sequencing analysis data demonstrated that expression levels of 3250, 3111, 3097, 3253 circRNAs were significantly altered at concentrations ranging from 1 to 10 µM MC-LR. Expression levels of hsa_circRNA_0000657 and hsa_circRNA_0000659 were down-regulated while hsa_circRNA_0003247 and hsa_circRNA_0001535 were up-regulated in all MC-LR-exposed groups. The high-throughput sequencing results of selected circRNAs differential expression genes (DEGs) levels were verified by real-time fluorescent quantitative PCR (qRT-PCR). Gene Ontology (GO) enrichment analysis showed that the functions of circRNAs significantly altered in HL7702 cells were predominantly associated with metabolism, systems development, and protein binding. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis data revealed that the target genes of differentially expressed circRNAs in HL7702 cells were involved in FoxO signaling pathway, protein processing in endoplasmic reticulum, Ras signaling pathway, cell cycle, PI3K-Akt signaling pathway, MAPK signaling pathway and pathways in cancer. In summary, evidence indicates that a correlation may exist between circRNAs and MC-LR-induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

Microcystin-LR (MC-LR) variant exposure poses a potential health hazard to ecosystem, animals, and humans. Previously investigators showed that autophagy plays a key role in MC-LR induced cytotoxicity immortalized murine ovarian granular KK-1 cells and rat Sertoli cells. Recently exposure to MC-LR via drinking water was reported to accumulate in mouse brain with associated adverse oxidant and inflammatory responses. However, autophagy the physiological mechanism required for cells to degrade their own impaired organelles to maintain their homeostasis has not been determined with respect to MC-LR actions on the central nervous system (CNS). Thus, the aim of this study was to examine the effects of MC-LR on autophagy using human neuroblastoma SK-N-SH cells as CNS model. Data demonstrated that after treatment with 15 or 30 µmol/L MC-LR for 48 hr significantly reduced survival rate was noted in SK-N-SH cells. MC-LR increased the expression levels of autophagy-related proteins light chain 3 (LC3) II/I and p62 in SK-N-SH cells, resulting in the accumulation of LC3 and increased intracellular free calcium ion levels. Data indicated that MC-LR induced adverse effects on the CNS as evidenced by decreased cellular survival associated with inhibition of autophagy flux and consequent enhanced autophagosomes accumulation. [ABSTRACT FROM AUTHOR]

The occurrence of microcystin-LR(MC-LR) variant a known hepatotoxin constitutes a global public health concern. However, the molecular mechanisms underlying MC-LR-induced hepatotoxicity remain to be determined. The aim of this study was to investigate whether long noncoding RNAs (lncRNA) were involved in MC-LR-mediated hepatotoxicity using human normal liver cell line HL7702 to profile lncRNAs after 24 hr treatment with MC-LR. With the use of high-throughput sequencing techniques, data showed that the expression levels of 37, 33, 34, 35 lncRNA were significantly altered following exposure to 1, 2.5, 5, or 10 μM MC-LR, respectively. In particular, the expression levels of LINC00847, MIR22HG and LNC_00027 were markedly increased in all treatment groups. It is of interest that LNC_00027 was identified as a novel lncRNA. Quantitative real-time PCR (qPCR) was employed to determine the differentially expressed lncRNA levels. Analysis using Gene Ontology (GO) enrichment identified the functions of target genes involved in systems development, metabolism, and protein binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that MC-LR exposure upregulated some important signaling pathways including pathway in cancer, PI3K-AKT signaling and MAPK pathway. In summary, data indicate that the MC-LR-induced alterations in lncRNA may be associated with hepatotoxicity and that upregulation of LINC00847, MIR22HG and LNC_00027 may play important roles in the observed MC-mediated liver damage. [ABSTRACT FROM AUTHOR]

Several studies previously demonstrated that microcystin (MC)-LR produced cytoskeletal damage, especially to actin filaments. However, the underlying mechanisms of MC-induced cytoskeletal reorganization remain to be determined. The aim of this study was to examine the effects of 5 or 10 µM MC-LR on microfilament depolarization and expression of microRNA-451a (miR-451a) which plays a crucial role in cellular processes including cell proliferation, apoptosis and tumorigenesis in HL7702 liver cells after 24 hr treatment. Data demonstrated that MC-LR increased microfilament depolarization, elevated phosphorylation levels of mitogen-activated protein kinase (MAPK/ERK1/2) and vasodilator-stimulated phosphoprotein (VASP) but lowered miR-451a RNA expression levels. These molecular processes were associated with no marked changes in total protein ERK1/2. Data demonstrate that transfection with miR-451a may not be effective in the presence of MC-LR as evidenced by the inability of excess microRNA to prevent toxin-induced inhibition of threonine protein phosphatases1 (PP1) and 2A (PP2A) and microfilament reorganization in HL7702 cells. [ABSTRACT FROM AUTHOR]