A novel （4-ferrocenylethyne） phenylamine functionalized graphene sheets （FEPA-GR）, coupling with chitosan （CS） were used as a signal amplification platform for simultaneous and sensitive determination of dopami...A novel （4-ferrocenylethyne） phenylamine functionalized graphene sheets （FEPA-GR）, coupling with chitosan （CS） were used as a signal amplification platform for simultaneous and sensitive determination of dopamine （DA） and acetaminophen （AC）. In this work, FEPA used as electron transfer mediator can be immobilized on GR surface via strong π-π stacking interaction between the conjugate chain of FEPA and GR, which effectively prevents FEPA electron mediator leaking from the electrode surface and amplified the signal. Transmission electron microscopy, FT-IR spectroscopy, UV-vis spectroscopy and electrochemical experiments results are all demonstrated the strong π-π stacking interaction between FEPA and GR. The resulted biosensor exhibited a fast response, remarkable electrocatalytic activity, perfect anti-interference ability and good stability for simultaneous detection of DA and AC. Under the optimum conditions, the oxidation peak currents of DA and AC were linearly correlated to their concentrations in the range of 2.0-135.0 μmol·L-1 and 0.3--80.0μmol·L 1, respectively. The lower detection limits for DA and AC were 0.30 and 0.05 μmol·L-1, respectively. The feasibility of the proposed method was validated by successfully applied to the simultaneous determination of DA and AC in serum samples with the standard addition method.展开更多
Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidati...Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic neurons.However,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely elucidated.NADPH oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains unknown.The aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what mechanism.We found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease model.NADPH oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic neurons.Moreover,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model animals.Mechanistically,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic neurons.Furthermore,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced neuroinflammation.These findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.展开更多
基金the National Natural Science Foundation of China，the Scientific Research Fund of Hunan Provincial Education Department，the Aid Program for Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Province
文摘A novel （4-ferrocenylethyne） phenylamine functionalized graphene sheets （FEPA-GR）, coupling with chitosan （CS） were used as a signal amplification platform for simultaneous and sensitive determination of dopamine （DA） and acetaminophen （AC）. In this work, FEPA used as electron transfer mediator can be immobilized on GR surface via strong π-π stacking interaction between the conjugate chain of FEPA and GR, which effectively prevents FEPA electron mediator leaking from the electrode surface and amplified the signal. Transmission electron microscopy, FT-IR spectroscopy, UV-vis spectroscopy and electrochemical experiments results are all demonstrated the strong π-π stacking interaction between FEPA and GR. The resulted biosensor exhibited a fast response, remarkable electrocatalytic activity, perfect anti-interference ability and good stability for simultaneous detection of DA and AC. Under the optimum conditions, the oxidation peak currents of DA and AC were linearly correlated to their concentrations in the range of 2.0-135.0 μmol·L-1 and 0.3--80.0μmol·L 1, respectively. The lower detection limits for DA and AC were 0.30 and 0.05 μmol·L-1, respectively. The feasibility of the proposed method was validated by successfully applied to the simultaneous determination of DA and AC in serum samples with the standard addition method.
基金supported by the National Natural Science Foundation of China,Nos.82271444(to JP),82271268(to BZ),and 82001346(to YL)the National Key Research and Development Program of China,No.2022YFE0210100(to BZ)。
文摘Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic neurons.However,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely elucidated.NADPH oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains unknown.The aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what mechanism.We found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease model.NADPH oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic neurons.Moreover,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model animals.Mechanistically,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic neurons.Furthermore,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced neuroinflammation.These findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.
