13 research outputs found

    Does α-Amino-β-methylaminopropionic Acid (BMAA) Play a Role in Neurodegeneration?

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    The association of α-amino-β-methylaminopropionic acid (BMAA) with elevated incidence of amyotrophic lateral sclerosis/Parkinson’s disease complex (ALS/PDC) was first identified on the island of Guam. BMAA has been shown to be produced across the cyanobacterial order and its detection has been reported in a variety of aquatic and terrestrial environments worldwide, suggesting that it is ubiquitous. Various in vivo studies on rats, mice, chicks and monkeys have shown that it can cause neurodegenerative symptoms such as ataxia and convulsions. Zebrafish research has also shown disruption to neural development after BMAA exposure. In vitro studies on mice, rats and leeches have shown that BMAA acts predominantly on motor neurons. Observed increases in the generation of reactive oxygen species (ROS) and Ca2+ influx, coupled with disruption to mitochondrial activity and general neuronal death, indicate that the main mode of activity is via excitotoxic mechanisms. The current review pertaining to the neurotoxicity of BMAA clearly demonstrates its ability to adversely affect neural tissues, and implicates it as a potentially significant compound in the aetiology of neurodegenerative disease. When considering the potential adverse health effects upon exposure to this compound, further research to better understand the modes of toxicity of BMAA and the environmental exposure limits is essential

    Climate change and regulation of hepatotoxin production in Cyanobacteria

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    Harmful, bloom-forming cyanobacteria (CyanoHABs) are occurring with increasing regularity in freshwater and marine ecosystems. The most commonly occurring cyanobacterial toxins are the hepatotoxic microcystin and nodularin. These cyclic hepta- and pentapeptides are synthesised nonribosomally by the gene products of the toxin gene clusters mcy and nda, respectively. Understanding of the regulation of hepatotoxin production is incomplete, although there is strong evidence supporting the roles of iron, light, higher nitrate availability and inorganic carbon in modulating microcystin levels. The majority of these studies have focused on the unicellular freshwater, microcystin-producing strain of Microcystis aeruginosa, with little attention being paid to terrestrial or marine toxin producers. This review intends to investigate the regulation of microcystin and nodularin production in unicellular and filamentous diazotrophic cyanobacteria against the background of changing climate conditions. Special focus is given to diazotrophic filamentous cyanobacteria, for example Nodularia spumigena, capable of regulating their nitrogen levels by actively fixing dinitrogen. By combining data from significant studies, an overall scheme of the regulation of toxin production is presented, focussing specifically on nodularin production in diazotrophs against the background of increasing carbon dioxide concentrations and temperatures envisaged under current climate change models. Furthermore, the risk of sustaining and spreading CyanoHABs in the future ocean is evaluated

    Excitotoxic potential of the cyanotoxin β-methyl-amino-l-alanine (BMAA) in primary human neurons

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    The toxicity of the cyanobacterial modified amino acid, BMAA, has been described in rat, mouse and leech neurons. Particular emphasis has been placed on the potential ability of BMAA to induce neuronal damage via excitotoxic mechanisms. Here we present data indicating that the effects observed on lower organisms are also evident in a human model. Our data indicates that BMAA induces increased intracellular Ca 2+ influx, DNA damage, mitochondrial activity, lactate dehydrogenase (LDH) release and generation of reactive oxygen species (ROS). The amelioration of LDH release in the presence of the N-methyl-d-aspartate (NMDA) receptor antagonist MK801 indicates that the neurotoxic effects of BMAA are mediated via NMDA receptor activation. Additionally, we have shown that BMAA induces the expression of neuronal nitric oxide synthase (nNOS) and caspase-3 indicating that it can stimulate apoptosis in human neurons, presumably via activation of NMDA receptors.7 page(s

    Genetic Variation of the Bloom-Forming Cyanobacterium Microcystis aeruginosa within and among Lakes: Implications for Harmful Algal Blooms

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    To measure genetic variation within and among populations of the bloom-forming cyanobacterium Microcystis aeruginosa, we surveyed a suite of lakes in the southern peninsula of Michigan that vary in productivity (total phosphorus concentrations of ∼10 to 100 μg liter(−1)). Survival of M. aeruginosa isolates from lakes was relatively low (i.e., mean of 7% and maximum of 30%) and positively related to lake total phosphorus concentration (P = 0.014, r(2) = 0.407, n = 14). In another study (D. F. Raikow, O. Sarnelle, A. E. Wilson, and S. K. Hamilton, Limnol. Oceanogr. 49:482-487, 2004), survival rates of M. aeruginosa isolates collected from an oligotrophic lake (total phosphorus of ∼10 μg liter(−1) and dissolved inorganic nitrogen:total phosphorus ratio of 12.75) differed among five different medium types (G test, P of <0.001), with higher survival (P = 0.003) in low-nutrient media (28 to 37% survival) than in high-nutrient media. Even with the relatively low isolate survivorship that could select against detecting the full range of genetic variation, populations of M. aeruginosa were genetically diverse within and among lakes (by analysis of molecular variance, Φ(sc) = 0.412 [Φ(sc) is an F-statistic derivative which evaluates the correlation of haplotypic diversity within populations relative to the haplotypic diversity among all sampled populations], P = 0.001), with most clones being distantly related to clones collected from lakes directly attached to Lake Michigan (a Laurentian Great Lake) and culture collection strains collected from Canada, Scotland, and South Africa. Ninety-one percent of the 53 genetically unique M. aeruginosa clones contained the microcystin toxin gene (mcyA). Genotypes with the toxin gene were found in all lakes, while four lakes harbored both genotypes possessing and genotypes lacking the toxin gene

    Global cellular responses to β-methyl-amino-L-alanine (BMAA) by olfactory ensheathing glial cells (OEC)

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    This study utilised a proteomics approach to identify any differential protein expression in a glial cell line, rat olfactory ensheathing cells (OECs), treated with the cyanotoxin β-methylamino-l-alanine (BMAA). Five proteins of interest were identified, namely Rho GDP-dissociation inhibitor 1 (RhoGDP1), Nck-associated protein 1 (NCKAP1), voltage-dependent anion-selective channel protein 1 (VDAC1), 3-hydroxyacyl-CoA dehydrogenase type-2 (3hCoAdh2), and ubiquilin-4 (UBQLN4). Four of these candidates, nuclear receptor subfamily 4 group A member 1 (Nur77), cyclophilin A (CyPA), RhoGDP1 and VDAC1, have been reported to be involved in cell growth. A microarray identified UBQLN4, palladin and CyPA, which have been implicated to have roles in excitotoxicity. Moreover, the NCKAP1, UBQLN4, CyPA and 3hCoAdh2 genes have been associated with abnormal protein aggregation. Differential expression of genes involved in mitochondrial activity, Nur77, 3hCoAdh2, VDAC1 and UBQLN4, were also identified. Confirmatory reverse transcription quantitative PCR (RT-qPCR) analysis of transcripts generated from the genes of interest corroborated the differential expression trends identified in the global protein analysis. BMAA induced cell cycle arrest in the G2/M phase of OEC and apoptosis after 48 h at concentrations of 250 μM and 500 μM. Collectively, this work advances our understanding of the mechanism of BMAA-mediated glial-toxicity in vitro.10 page(s

    On the trail of iron uptake in ancestral Cyanobacteria on early Earth

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    This project was funded by the German Research Foundation SPP1833, DFG, Grant numbers: GE2558/3-1 & GE2558/4-1 awarded to MMG, a University of Bristol Graduate Teaching Scholarship awarded to J.S.B. and a Royal Society University Research Fellowship awarded to P.S-B. Open Access funding enabled and organized by Projekt DEAL.Cyanobacteria oxygenated Earth's atmosphere ~2.4 billion years ago, during the Great Oxygenation Event (GOE), through oxygenic photosynthesis. Their high iron requirement was presumably met by high levels of Fe(II) in the anoxic Archean environment. We found that many deeply branching Cyanobacteria, including two Gloeobacter and four Pseudanabaena spp., cannot synthesize the Fe(II) specific transporter, FeoB. Phylogenetic and relaxed molecular clock analyses find evidence that FeoB and the Fe(III) transporters, cFTR1 and FutB, were present in Proterozoic, but not earlier Archaean lineages of Cyanobacteria. Furthermore Pseudanabaena sp. PCC7367, an early diverging marine, benthic strain grown under simulated Archean conditions, constitutively expressed cftr1, even after the addition of Fe(II). Our genetic profiling suggests that, prior to the GOE, ancestral Cyanobacteria may have utilized alternative metal iron transporters such as ZIP, NRAMP, or FicI, and possibly also scavenged exogenous siderophore bound Fe(III), as they only acquired the necessary Fe(II) and Fe(III) transporters during the Proterozoic. Given that Cyanobacteria arose 3.3-3.6 billion years ago, it is possible that limitations in iron uptake may have contributed to the delay in their expansion during the Archean, and hence the oxygenation of the early Earth.Publisher PDFPeer reviewe

    On the trail of iron uptake in ancestral Cyanobacteria on early Earth

    No full text
    Cyanobacteria oxygenated Earth's atmosphere ~2.4 billion years ago, during the Great Oxygenation Event (GOE), through oxygenic photosynthesis. Their high iron requirement was presumably met by high levels of Fe(II) in the anoxic Archean environment. We found that many deeply branching Cyanobacteria, including two Gloeobacter and four Pseudanabaena spp., cannot synthesize the Fe(II) specific transporter, FeoB. Phylogenetic and relaxed molecular clock analyses find evidence that FeoB and the Fe(III) transporters, cFTR1 and FutB, were present in Proterozoic, but not earlier Archaean lineages of Cyanobacteria. Furthermore Pseudanabaena sp. PCC7367, an early diverging marine, benthic strain grown under simulated Archean conditions, constitutively expressed cftr1, even after the addition of Fe(II). Our genetic profiling suggests that, prior to the GOE, ancestral Cyanobacteria may have utilized alternative metal iron transporters such as ZIP, NRAMP, or FicI, and possibly also scavenged exogenous siderophore bound Fe(III), as they only acquired the necessary Fe(II) and Fe(III) transporters during the Proterozoic. Given that Cyanobacteria arose 3.3–3.6 billion years ago, it is possible that limitations in iron uptake may have contributed to the delay in their expansion during the Archean, and hence the oxygenation of the early Earth.Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659Royal Society of Biology http://dx.doi.org/10.13039/100012361University of Bristol http://dx.doi.org/10.13039/501100000883https://osf.io/7x598/?view_only=715cd38c378446ba8c3f6c924f9be9f
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