Disease relevance of Toxin-LR

• Microcystin, a hepatotoxin that represents a serious health risk for humans and livestock, is produced by the bloom-forming cyanobacterium Microcystis aeruginosa in freshwater bodies worldwide [1].
• Microcystis aeruginosa toxin: cell culture toxicity, hemolysis, and mutagenicity assays [2].
• Acute, severe thrombocytopenia, a characteristic of cyanoginosin-LR toxicity, remains unexplained since platelets did not concentrate in the lungs, liver, or spleen [3].
• Toxin-LR, a hexapeptide produced by Microcystis aeruginosa, causes marked hepatic vascular congestion, thrombocytopenia, microscopic pulmonary thrombi and death in 50-70 min when injected into mice [4].
• Young adult mice consuming up to 333 microg MCLR/kg body weight (bw)/day exhibited no adverse effects on growth and reproduction, fetal development, and survival and organ weights of neonates [5].

High impact information on Toxin-LR

• We obtained similar results in pull-down experiments with immobilized Microcystin, a PP2A inhibitor [6].
• Subsequent addition of 4 microM microcystin, a potent inhibitor of type 1 and type 2A protein phosphatases, induced a rapid inactivation of glycogen synthase, which occurred at a similar rate in all three types of hepatocytes [7].
• A rapid competitive binding nonseparation electrochemical enzyme immunoassay (NEEIA) test strip for microcystin-LR (MCLR) determination [8].
• Both ALLN and ALLM, two calpain inhibitors, significantly blocked MLR-induced calpain activation and subsequent cell death [9].
• Instead, MLR activated calpain in rat hepatocytes, probably through the increase of intracellular Ca(2+) released from mitochondria [9].

Biological context of Toxin-LR

• CsA also prevented MLR-induced calpain activation and cell death, suggesting that the activation of calpain may be a post-mitochondrial event [9].
• Various mitochondrial electron transport chain (ETC) inhibitors effectively prevented the onset of MPT, suggesting that the mitochondrial ETC plays an important role in MLR-induced MPT [9].
• These data demonstrate for the first time that calpain rather than caspases plays an important role in MLR-induced apoptosis [9].
• Microcystin, a worldwide common cyanobacterial hepatotoxin, was the first metabolite whose nonribosomal biosynthesis could be confirmed by knock-out mutagenesis [10].
• In vitro platelet aggregation or lysis did not occur during incubation with toxin-LR, nor was a humoral aggregating factor detected in plasma from toxin-injected mice [4].

Anatomical context of Toxin-LR

• This suggests that Microcystis aeruginosa toxin is transported into hepatocytes in the same way as phalloidin; namely sharing a transport system for bile acids on the hepatocyte plasma membrane [11].
• The application of microcystin, a potent protein phosphatase inhibitor, induced a tonic contraction of skinned smooth muscle at low Ca2+ concentration ([Ca2+]; pCa > 8.0) [12].

Associations of Toxin-LR with other chemical compounds

• In primary rat hepatocyte cultures, all MAbs showed protective effects against the MCLR-induced cell damages, assessed by morphological changes, lactate dehydrogenase release into the medium, and a calorimetric assay to measure the cell viability using a tetrazolium dye [13].
• Spectral changes exhibited by the binding of MLR, VLM and ENB to dansyl-CaM as compared to that of CSA and GRS reflected different binding sites and/or different conformational changes [14].

Gene context of Toxin-LR

• ELISA and immunoprecipitation analysis revealed that Id7 specifically bound to MAb-mc but not to control IgG1, and the binding was inhibited by free MCLR [15].

Analytical, diagnostic and therapeutic context of Toxin-LR

• Three IC MAbs were obtained, all of which specifically reacted with the IC, but almost never reacted to MC MAb or MCLR in enzyme-linked immunosorbent assays (ELISAs) [16].
• Intracellular perfusion with microcystin, a potent phosphatase 1 and 2a inhibitor, increased both endogenous and exogenous AMPA receptor-mediated currents, further supporting a role of phosphorylation in modulating motoneuronal excitability affecting behaviorally relevant synaptic inputs [17].

References