Current trends and patterns of PFAS in agroecosystems and environment: A review.

Per- and polyfluoroalkyl substances (PFASs) are one of the more well-known highly persistent organic pollutants with potential risks to agroecological systems. These compounds are of global concern due to their persistence and mobility, and they often lead to serious impacts on environmental, agricultural, and human health. In the past 20 years, the number of science publications on PFAS has risen; despite this, certain fundamental questions about PFAS occurrence, sources, mechanism of transport, and impacts on agroecosystems and the societies dependent on them are still open and evolving.

Brevetoxin induces a shift in the redox state of the proteome and unfolded protein response in human lymphoblast cells that can be alleviated with the acrolein scavenger MESNA.

Human lymphoblast cells were treated with the marine algal toxin, brevetoxin-2 (PbTx-2), and its effects on the proteome were assessed by redox proteomics using cysteine reactive tandem mass tags (TMT). Additionally, cells were simultaneously treated with PbTx-2 and the antioxidant and acrolein scavenger sodium 2-mercaptoethylsulfonate (MESNA) to determine if MESNA could prevent the proteomic effects of brevetoxin-2. A massive shift in the redox state of the proteome of brevetoxin-2 treated cells was observed.

The Marine Neurotoxin Brevetoxin (PbTx-2) Inhibits and Mammalian Thioredoxin Reductases by Targeting Different Residues.

The brevetoxins, neurotoxins produced by , the Florida red tide dinoflagellate, effect fish and wildlife mortalities and adverse public health and economic impacts during recurrent blooms. Knowledge of the biochemical consequences of toxin production for could provide insights into an endogenous role of the toxins, yet this aspect has not been thoroughly explored. In addition to neurotoxicity, the most abundant of the brevetoxins, PbTx-2, inhibits mammalian thioredoxin reductase (TrxR).

Essential components of the xanthophyll cycle differ in high and low toxin Karenia brevis.

The dinoflagellate Karenia brevis, blooms annually in the Gulf of Mexico, producing a suite of neurotoxins known as the brevetoxins. The cellular toxin content of K. brevis, however, is highly variable between or even within strains.

Effectors of thioredoxin reductase: Brevetoxins and manumycin-A.

The activities of two effectors, brevetoxin (PbTx) and manumycin-A (Man-A), of thioredoxin reductase (TrxR) have been evaluated against a series of fourteen TrxR orthologs originating from mammals, insects and protists and several mutants. Man-A, a molecule with numerous electrophilic sites, forms a covalent adduct with most selenocystine (Sec)-containing TrxR enzymes. The evidence also demonstrates that Man-A can form covalent adducts with some non-Sec-containing enzymes.

Manumycin A Is a Potent Inhibitor of Mammalian Thioredoxin Reductase-1 (TrxR-1).

The anticancer effect of manumycin A (Man A) has been attributed to the inhibition of farnesyl transferase (FTase), an enzyme that is responsible for post-translational modification of proteins. However, we have discovered that Man A inhibits mammalian cytosolic thioredoxin reductase 1 (TrxR-1) in a time-dependent manner, with an IC of 272 nM with preincubation and 1586 nM without preincubation. The inhibition of TrxR-1 by Man A is irreversible and is the result of a covalent interaction between Man A and TrxR-1.

Brevetoxin (PbTx-2) influences the redox status and NPQ of Karenia brevis by way of thioredoxin reductase.

The Florida red tide dinoflagellate, Karenia brevis, is the major harmful algal bloom dinoflagellate of the Gulf of Mexico and plays a destructive role in the region. Blooms of K. brevis can produce brevetoxins: ladder-shaped polyether (LSP) compounds, which can lead to adverse human health effects, such as reduced respiratory function through inhalation exposure, or neurotoxic shellfish poisoning through consumption of contaminated shellfish.

Toxin composition of the 2016 Microcystis aeruginosa bloom in the St. Lucie Estuary, Florida.

A bloom of the cyanobacteria, Microcystis aeruginosa occurred in the St. Lucie Estuary during the summer of 2016, stimulated by the release of waters from Lake Okeechobee. This cyanobacterium produces the microcystins, a suite of heptapeptide hepatotoxins.

Brevetoxin-2, is a unique inhibitor of the C-terminal redox center of mammalian thioredoxin reductase-1.

Karenia brevis, the Florida red tide dinoflagellate produces a suite of neurotoxins known as the brevetoxins. The most abundant of the brevetoxins PbTx-2, was found to inhibit the thioredoxin-thioredoxin reductase system, whereas the PbTx-3 has no effect on this system. On the other hand, PbTx-2 activates the reduction of small disulfides such as 5,5'-dithio-bis-(2-nitrobenzoic acid) by thioredoxin reductase.

Metabolism of okadaic acid by NADPH-dependent enzymes present in human or rat liver S9 fractions results in different toxic effects.

The lipophilic marine biotoxin okadaic acid (OA) represents a natural contaminant produced by algae accumulating in seafood. Acute intoxications result in diarrhetic shellfish poisoning causing symptoms like nausea, vomiting and abdominal cramps. OA was preincubated with liver enzymes present in S9 fractions from humans, rats and rats pretreated with enzyme inducers in the presence or absence of the cofactor NADPH to investigate hepatic metabolism.

Characterization of an epoxide hydrolase from the Florida red tide dinoflagellate, Karenia brevis.

Epoxide hydrolases (EH, EC 3.3.2.

Differences in metabolism of the marine biotoxin okadaic acid by human and rat cytochrome P450 monooxygenases.

The ingestion of seafood contaminated with the marine biotoxin okadaic acid (OA) can lead to diarrhetic shellfish poisoning with symptoms like nausea, vomiting and abdominal cramps. Both rat and the human hepatic cytochrome P450 monooxygenases (CYP) metabolize OA. However, liver cell toxicity of metabolized OA is mainly unclear.

Brevetoxin, the Dinoflagellate Neurotoxin, Localizes to Thylakoid Membranes and Interacts with the Light-Harvesting Complex II (LHCII) of Photosystem II.

The brevetoxins are neurotoxins that are produced by the "Florida red tide" dinoflagellate Karenia brevis. They bind to and activate the voltage-gated sodium channels in higher organisms, specifically the Nav 1.4 and Nav 1.

Subcellular localization of dinoflagellate polyketide synthases and fatty acid synthase activity.

Dinoflagellates are prolific producers of polyketide secondary metabolites. Dinoflagellate polyketide synthases (PKSs) have sequence similarity to Type I PKSs, megasynthases that encode all catalytic domains on a single polypeptide. However, in dinoflagellate PKSs identified to date, each catalytic domain resides on a separate transcript, suggesting multiprotein complexes similar to Type II PKSs.

Synthesis, receptor binding and activity of iso and azakainoids.

Two syntheses for the production of an unsubstituted azakainoid are described. The 1,3-dipolar cycloaddition of diazomethane with trans-dibenzyl glutaconate yields a 1-pyrazoline, which may be reduced directly to the pyrazolidine. An unexpected trans-cis isomerization is observed during Hg/Al reduction of the 1-pyrazoline NN bond.

GENE EXPRESSION PROFILING OF HUMAN LIVER CARCINOMA (HepG2) CELLS EXPOSED TO THE MARINE TOXIN OKADAIC ACID.

The marine toxin, okadaic acid (OA) is produced by dinoflagellates of the genera Prorocentrum and Dinophysis and is the causative agent of the syndrome known as diarrheic shellfish poisoning (DSP). In addition, OA acts as both a tumor promoter, attributed to OA-induced inhibition of protein phosphatases as well as an inducer of apoptosis. To better understand the potentially divergent toxicological profile of OA, the concentration dependent cytotoxicity and alterations in gene expression on the human liver tumor cell line HepG2 upon OA exposure were determined using RNA microarrays, DNA fragmentation, and cell proliferation assays as well as determinations of cell detachment and cell death in different concentrations of OA.

Biosynthesis of Athmu, a α,γ-hydroxy-β-amino acid of pahayokolides A-B.

Pahayokolides A-B are cyanobacteria derived non-ribosomal peptides which exhibit cytotoxicity against a number of cancer cell lines. The biosynthetic origin of the 3-amino-2,5,7,8-tetrahydroxy-10-methylundecanoic acid (Athmu) moiety has been investigated using stable isotope incorporation experiments. While α-ketoisocaproic acid (α-KIC), α-hydroxyisocaproic acid (α-HIC) and leucine all serve as precursors to Athmu, the feeding of [1-(13)C] α-KIC results in more than threefold greater (13)C enrichment than the other precursors.

The structures of three metabolites of the algal hepatotoxin okadaic acid produced by oxidation with human cytochrome P450.

Four metabolites of okadaic acid were generated by incubation with human recombinant cytochrome P450 3A4. The structures of two of the four metabolites have been determined by MS/MS experiments and 1D and 2D NMR methods using 94 and 133 μg of each metabolite. The structure of a third metabolite was determined by oxidation to a metabolite of known structure.

Biosynthetic origin of the 3-amino-2,5,7,8-tetrahydroxy-10-methylundecanoic acid moiety and absolute configuration of pahayokolides A and B.

Pahayokolides A and B are cyclic undecapeptides that were isolated from the cyanobacterium Lyngbya sp. They contain the unusual α-hydroxy-β-amino acid 3-amino-2,5,7,8-tetrahydroxy-10-methylundecanoic acid (Athmu). The absolute configurations of the amino acids of the pahayokolides, except for the four oxygen-bearing stereocenters of Athmu, have been determined by Marphy's method.

Biodegradation of polyether algal toxins--isolation of potential marine bacteria.

Marine algal toxins such as brevetoxins, okadaic acid, yessotoxin, and ciguatoxin are polyether compounds. The fate of polyether toxins in the aqueous phase, particularly bacterial biotransformation of the toxins, is poorly understood. An inexpensive and easily available polyether structural analog salinomycin was used for enrichment and isolation of potential polyether toxin degrading aquatic marine bacteria from Florida bay area, and from red tide endemic sites in the South Florida Gulf coast.

New peptides isolated from Lyngbya species: a review.

Cyanobacteria of the genus Lyngbya have proven to be prodigious producers of secondary metabolites. Many of these compounds are bioactive and show potential for therapeutic use. This review covers peptides and hybrid polyketide-non-ribosomal peptides isolated from Lyngbya species.

Human metabolites of brevetoxin PbTx-2: Identification and confirmation of structure.

Four metabolites were identified upon incubation of brevetoxin (PbTx-2) with human liver microsomes. Chemical transformation of PbTx-2 confirmed the structures of three known metabolites BTX-B5, PbTx-9 and 41, 43-dihydro-BTX-B5 and a previously unknown metabolite, 41, 43-dihydro-PbTx-2. These metabolites were also observed upon incubation of PbTx-2 with nine human recombinant cytochrome P450s (1A1, 1A2, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4 and 3A5).

Viable cell sorting of dinoflagellates by multiparametric flow cytometry.

Electronic cell sorting for isolation and culture of dinoflagellates and other marine eukaryotic phytoplankton was compared to the traditional method of manually picking cells using a micropipette. Trauma to electronically sorted cells was not a limiting factor, as fragile dinoflagellates, such as Karenia brevis (Dinophyceae), survived electronic cell sorting to yield viable cells. The rate of successful isolation of large-scale (> 4 litres) cultures was higher for manual picking than for electronic cell sorting (2% vs 0.

UV and solar TiO(2) photocatalysis of brevetoxins (PbTxs).

Karenia brevis, the harmful alga associated with red tide, produces brevetoxins (PbTxs). Exposure to these toxins can have a negative impact on marine wildlife and serious human health consequences. The elimination of PbTxs is critical to protect the marine environment and human health.

Identification of okadaic acid production in the marine dinoflagellate Prorocentrum rhathymum from Florida Bay.

Extracts of fifty-seven newly isolated strains of dinoflagellates and raphidophytes were screened for protein phosphatase (PP2A) inhibition. Five strains, identified by rDNA sequence analysis as Prorocentrum rhathymum, tested positive and the presence of okadaic acid was confirmed in one strain by HPLC-MS/MS and by HPLC with fluorescence detection and HPLC-MS of the okadaic acid ADAM derivative. Quantitation of the ADAM derivative indicated that the concentration of okadaic acid in the culture medium is 0.