Yessotoxin (YTX) and its analogues are disulphated polyether compounds of increasing occurrence in seafood. The biological effects of these algal toxins on mammals and the risk associated to their ingestion have not been clearly established. We have used primary cultures of rat cerebellar neurons to investigate whether YTX affected survival and functioning of central nervous system neurons. Exposure to YTX (> or =25 nM) caused first (approximately 8 h) weakening, granulation, and fragmentation of neuronal network, and later (approximately 48 h) complete disintegration of neurites and extensive neuronal death, with a significant decrease in the amount of filamentous actin. The concentration of YTX that reduced by 50% the maximum neuronal survival (EC50(48)) was approximately 20 nM. Lower toxin concentrations (approximately 15 nM) also caused visible signs of toxicity affecting neuronal network primarily. Removal of YTX after 5 h exposure delayed the onset of neurotoxicity but did not prevent neuronal degeneration and death. YTX induced a two-fold increase in cytosolic calcium that was prevented by the voltage-sensitive calcium channel antagonists nifedipine and verapamil. These antagonists were, however, completely ineffective in reducing neurotoxicity. Voltage-sensitive sodium channel antagonists saxitoxin and nefopam, and the NMDA receptor antagonist MK-801 also failed to prevent YTX neurotoxicity. Neuronal death by YTX involved typical hallmarks of apoptosis and required the synthesis of new proteins. Our data suggest neuronal tissue to be a vulnerable biological target for YTX. The potent neurotoxicity of YTX we report raises reasonable concern about the potential risk that exposure to YTX may represent for neuronal survival in vivo.
We have investigated the ability of bFGF to protect cerebellar neurons from neurotoxicity by excitatory amino acids. We have found that preincubation with l-2.5 nM bFGF for l-6 days significantly protected neurons from excitotoxic damage via NMDA receptors as well as ionotropic non-NMDA receptors. bFGF neuroprotection appeared not to be dependent upon neuronal differentiation and was not mimicked by other neurotrophins including BDNF. NT-3 and NGF. A greater rise in extracellular calcium-dependent cGMP formation, following either depolarization or excitatory amino acid receptor activation was observed in bFGF-pretreated neurons. We suggest that neuroprotection from excitotoxicity following bFGF treatment may be associated to the modulation of neurochemical pathways dependent upon extracellular calcium influx.
In this work, bifunctional core@shell Au@Pt/Au NPs are presented as novel tags for electrochemical immunosensing.Au@Pt/Au NPs were synthesized following a chemical route based on successive metal depositions and galvanic replacement reactions from the starting AuNPs. Au protuberances growth on the surface of Au@Pt NPs allowed their easy bioconjugation with antibodies, while the high catalytic Pt surface area was approached for their sensitive detection through the electrocatalysed water oxidation reaction (WOR) at neutral pH. Moreover, the synergy between Au and Pt metals on the NP surface also lead to an increased catalytic activity, improving the sensitivity of the NP detection. Cyclic voltammetry and chronoamperometry were used for the evaluation of the Au@Pt/Au NPs electrocatalytic activity towards WOR. The chronoamperometric current recorded at a fixed potential of +1.35 V was selected as the analytical signal, allowing the quantification of Au@Pt/Au NPs at 10 13 NPs/mL levels. The optimized electrocatalytic method was applied to the quantification of conformationally altered p53 peptide Alzheimer's disease (AD) biomarker in a competitive immunoassay using magnetic bead (MB) platforms at levels as low as 66 nM. The performance of the system in a real scenario was demonstrated analysing plasma samples from a cognitively healthy subject. This novel Au@Pt/Au NPs-based electrocatalytic immunoassay has the advantage, over common methods for NP tags electrochemical detection, of the signal generation in the same neutral medium where the immunoassay takes place (0.1 M PBS pH 7.2), avoiding the use of additional and more hazardous reagents and paving the way to future integrated biosensing systems. 38 trolled synthesis, higher stability against harsh conditions, 39 higher resistance to high concentrations of substrate and a lower 40 cost [3][4][5][6] . The use of electrocatalytic NPs as labels has been ex-41 tensively studied and applied in immunosensing [7][8][9][10][11][12] , offering 42 outstanding alternatives to traditional assays. 43Among the wide variety of NPs, metallic NP labels have at-44 tracted considerable interest due to their unique red-ox and op-45 tical properties 13,14 as well as their electrocatalytic activity, also 46 benefiting of the inherent advantages of the electrochemical de-47 tection in terms of sensitivity, selectivity, simplicity and low 48 cost 15 . In most cases highly acidic media are needed for such 49 NPs detection, either to facilitate dissolution 16 or as source of 50 hydrogen ions for further detection based on hydrogen evolu-51 tion reaction (HER) [17][18][19][20][21][22][23] . However, the use of acid solutions is 52 not desirable for both safety reasons and the time needed for the 53 analysis, also involving additional steps after the immunoassay. 54Consequently, there is a need of NP tags that may be detected 55 in the same medium where immunoreactions take place. In this 56 context, the water oxidation reaction (WOR) occurring at neu-57 tral pH and easily catalysed by some ...
Belizentrin (1), a novel 25-membered polyketide-derived macrocycle, was isolated from cultures of the marine dinoflagellate Prorocentrum belizeanum. This metabolite is the first member of an unprecedented class of polyunsaturated and polyhydroxylated macrolactams. The structure of 1 was primarily determined by NMR and computational methods. Pharmacological assays with cerebellar cells showed that 1 produces important changes in neuronal network integrity at nanomolar concentrations.
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