Aging is a physiological process that leads to degeneration and functional decline of the brain.This is accompanied by intracellular peroxidation and neuronal apoptosis.Natural antioxidants possess a remarkable effect...Aging is a physiological process that leads to degeneration and functional decline of the brain.This is accompanied by intracellular peroxidation and neuronal apoptosis.Natural antioxidants possess a remarkable effect on attenuating the oxidative stress cascade and apoptosis of neurons;however,the challenge of using natural antioxidants for neuroprotection is fabricating a delivery system to overcome the blood-brain barrier(BBB)transport.Herein,we successfully created a stable delivery platform built on rigid ferritin nanocage loading natural lycopene molecules,crossing the BBB in quantity and being taken up in neurons.This nanoparticle worked on D-galactose-induced senescence via alleviating neuronal hyperoxidation injury and weakening neuronal apoptosis in PC12 and BV2 cells.More importantly,this natural delivery system possesses inherent biocompatibility and potential application in improving the bioavailability of bioactive edible compounds with low water solubility.This study demonstrated the effectiveness of natural antioxidant nanomedicines in maintaining the defenses of intracerebral peroxidation and improve degenerating neurons,providing the potential to combat further imbalances of neuronal microenvironment in aging neuropathy.展开更多
AIM:To study the role of hepcidin in hereditary hyperferritinemia cataract syndrome(HHCS). METHODS:Six patients from two families with HHCS, confirmed by genetic analysis showing A to G mutation at position+40 in the ...AIM:To study the role of hepcidin in hereditary hyperferritinemia cataract syndrome(HHCS). METHODS:Six patients from two families with HHCS, confirmed by genetic analysis showing A to G mutation at position+40 in the L-ferritin gene,were recruited to undergo serum hepcidin and prohepcidin measurements using radioimmunoassay and enzyme linked immunoassay,respectively,and measurements were compared with levels in serum from 25 healthy volunteers(14 females),mean age 36±11.9 years.RESULTS:The serum hepcidin and prohepcidin levels in patients with HHCS were 19.1±18.6 and 187± 120.9 ng/mL,respectively.Serum ferritin was 1716.3± 376μg/L.Liver biopsy in one patient did not show any evidence of iron overload.Serum hepcidin and prohepcidin values in healthy controls(HCs)were 15.30±15.71 and 236.88±83.68 ng/mL,respectively,while serum ferritin was 110±128.08μg/L.There was no statistical difference in serum hepcidin level between the two cohorts(19.1±18.6 ng/mL vs 15.30±15.71 ng/mL,P= 0.612)using two-tailed t-test. CONCLUSION:Serum hepcidin levels in HHCS patients is similar to that in HCs.Our study suggests that circulating ferritin is not a factor influencing hepcidin synthesis and does not have a role in the iron-sensing mechanism in hepatocytes.展开更多
According to the conserved sequence of the ferritin gene, a homologous sequence was obtained from the EST database through a BLAST search against the GenBank database. This sequence was amplified with the method of RT...According to the conserved sequence of the ferritin gene, a homologous sequence was obtained from the EST database through a BLAST search against the GenBank database. This sequence was amplified with the method of RT-PCR, false sequencing was corrected, and full length eDNA of the ferritin subunit from the Chinese sturgeon was obtained. After being submitted to the GenBank database, the sequence accession number EU348782 was assigned. With the length of 896 bp, this eDNA includes entire coding regions of 53 lbp, which encodes 176 amino acids （aa）. The molecular weight was predicted to be 20339.9Mr and the theoretical isoelectric point 5.66. It shares 82.9% protein sequence homology with the ferritin of the Atlantic salmon. This gene is expressed in many organs of the Chinese sturgeon, for example, the liver, pancreas, muscle, brain, heart and gastric mucosa. The highest expression level was found in the pancreas and the heart, while the muscular tissue showed the lowest. Homology modeling was used to predict the 3-D structure of the protein, which included 5 alpha helices and 10 turns. The ferritin protein structure could be overlapped and showed high similarity with that of human, flog and bacteria. It was revealed that this kind of ferritin was highly conserved in structure and function.展开更多
OBJECTIVE:To explore the effect of acupuncture treatment on cerebral ischaemia-reperfusion injury(CIRI)and reveal the underlying mechanism of the effect based on nuclear receptor coactivator 4(NCOA4)mediated ferritino...OBJECTIVE:To explore the effect of acupuncture treatment on cerebral ischaemia-reperfusion injury(CIRI)and reveal the underlying mechanism of the effect based on nuclear receptor coactivator 4(NCOA4)mediated ferritinophagy.METHODS:Sprague-Dawley male rats were divided into four groups:the sham group,model group,acupuncture group,and sham acupuncture group.After 2 h of middle cerebral artery occlusion(MCAO),reperfusion was performed for 24 h to induce CIRI.The rats were treated with acupuncture at the Neiguan(PC6)and Shuigou(GV26)acupoints.Their neurological function was evaluated by taking their Bederson scores at 2 h after ischaemia and 24 h after reperfusion.Triphenyltetrazolium chloride staining was applied to assess the cerebral infarct volume at 24 h after reperfusion.The malondialdehyde(MDA)and ferrous iron(Fe^(2+))levels were observed after 24 h of reperfusion using an assay kit.Western blotting was performed to detect the expression of NCOA4 and ferritin heavy chain 1(FTH1)at 24 h after reperfusion.Moreover,the colocalization of ferritin with neurons,NCOA4 with microtubule-associated protein 1 light chain 3(LC3),and NCOA4 with ferritin was visualized using immunofluorescence staining.RESULTS:Acupuncture significantly improved neurological function and decreased cerebral infarct volume in the acupuncture group.Following CIRI,the expression of NCOA4,LC3 and FTH1 was increased,which enhanced ferritinophagy and induced an inappropriate accumulation of Fe^(2+)and MDA in the ischaemic brain.However,acupuncture dramatically downregulated the expression of NCOA4,LC3 and FTH1,inhibited the overactivation of ferritinophagy,and decreased the levels of MDA and Fe^(2+).CONCLUSIONS:Acupuncture can inhibit NCOA4-mediated ferritinophagy and protect neurons against CIRI in a rat model.展开更多
Animal cells require extrinsic cues for growth, proliferation and survival. The propagation of Drosophila imaginal disc cells in vitro, for example, requires the supplementation of fly extract, the composition of whic...Animal cells require extrinsic cues for growth, proliferation and survival. The propagation of Drosophila imaginal disc cells in vitro, for example, requires the supplementation of fly extract, the composition of which remains largely undefined. Here I report the biochemical purification of iron-loaded ferritin as an active ingredient of fly extract that is required for promoting the growth of clone 8 imaginal disc cells. Consistent with an essential role for iron- loaded ferritin in cultured cells, overexpression of ferritin or addition of iron in a nutrient-poor diet increases animal viability and body weight, promotes cell proliferation, and shortens the duration of postembryonic development. Conversely, overexpression of dominant-negative ferritin or addition of iron chelator causes the opposite effects. Fer- ritin mutant flies arrest development at the first-instar larval stage with a severe starvation phenotype reminiscent of that seen in starved larvae. I conclude that iron-loaded ferritin acts as an essential mitogen for cell proliferation and postembryonic development in Drosophila by maintaining iron homeostasis and antagonizing starvation response.展开更多
Ferritins can generally be divided into four subfamilies based on their structural characteristics,namely,the classic ferritins(Ftns),bacterioferritins(Bfrs),DNA-binding proteins from starved cells(Dps’),and encapsul...Ferritins can generally be divided into four subfamilies based on their structural characteristics,namely,the classic ferritins(Ftns),bacterioferritins(Bfrs),DNA-binding proteins from starved cells(Dps’),and encapsulated ferritins(Enc Ftns).However,the ferritin from Mycoplasma penetrans(Mpef)possesses a particular ferroxidase center with an extreme low activity and exhibits unusual characteristics,indicating that it could be a member of a quite different subfamily of ferritins.Hereby,the crystal structure of the ferritin from Ureaplasma urealyticum(Uurf)is presented,Mpef and Uurf have very similar properties,though they display very low sequence similarity.Thus,ferritins from Mycoplasma with these unique properties do not belong to any known subfamily,but they should rather be placed in a novel ferritin subfamily,which we term Mycoplasma Ferritin(Mfr).展开更多
基金financially supported by the National Natural Science Foundation of China(31730069)Graduate Innovation Fund of Dalian Polytechnic University。
文摘Aging is a physiological process that leads to degeneration and functional decline of the brain.This is accompanied by intracellular peroxidation and neuronal apoptosis.Natural antioxidants possess a remarkable effect on attenuating the oxidative stress cascade and apoptosis of neurons;however,the challenge of using natural antioxidants for neuroprotection is fabricating a delivery system to overcome the blood-brain barrier(BBB)transport.Herein,we successfully created a stable delivery platform built on rigid ferritin nanocage loading natural lycopene molecules,crossing the BBB in quantity and being taken up in neurons.This nanoparticle worked on D-galactose-induced senescence via alleviating neuronal hyperoxidation injury and weakening neuronal apoptosis in PC12 and BV2 cells.More importantly,this natural delivery system possesses inherent biocompatibility and potential application in improving the bioavailability of bioactive edible compounds with low water solubility.This study demonstrated the effectiveness of natural antioxidant nanomedicines in maintaining the defenses of intracerebral peroxidation and improve degenerating neurons,providing the potential to combat further imbalances of neuronal microenvironment in aging neuropathy.
基金Supported by Research and Development Department,Ealing Hospital NHS Trust,Uxbridge Road,Southall,London,UB13HW,United Kingdom
文摘AIM:To study the role of hepcidin in hereditary hyperferritinemia cataract syndrome(HHCS). METHODS:Six patients from two families with HHCS, confirmed by genetic analysis showing A to G mutation at position+40 in the L-ferritin gene,were recruited to undergo serum hepcidin and prohepcidin measurements using radioimmunoassay and enzyme linked immunoassay,respectively,and measurements were compared with levels in serum from 25 healthy volunteers(14 females),mean age 36±11.9 years.RESULTS:The serum hepcidin and prohepcidin levels in patients with HHCS were 19.1±18.6 and 187± 120.9 ng/mL,respectively.Serum ferritin was 1716.3± 376μg/L.Liver biopsy in one patient did not show any evidence of iron overload.Serum hepcidin and prohepcidin values in healthy controls(HCs)were 15.30±15.71 and 236.88±83.68 ng/mL,respectively,while serum ferritin was 110±128.08μg/L.There was no statistical difference in serum hepcidin level between the two cohorts(19.1±18.6 ng/mL vs 15.30±15.71 ng/mL,P= 0.612)using two-tailed t-test. CONCLUSION:Serum hepcidin levels in HHCS patients is similar to that in HCs.Our study suggests that circulating ferritin is not a factor influencing hepcidin synthesis and does not have a role in the iron-sensing mechanism in hepatocytes.
文摘According to the conserved sequence of the ferritin gene, a homologous sequence was obtained from the EST database through a BLAST search against the GenBank database. This sequence was amplified with the method of RT-PCR, false sequencing was corrected, and full length eDNA of the ferritin subunit from the Chinese sturgeon was obtained. After being submitted to the GenBank database, the sequence accession number EU348782 was assigned. With the length of 896 bp, this eDNA includes entire coding regions of 53 lbp, which encodes 176 amino acids （aa）. The molecular weight was predicted to be 20339.9Mr and the theoretical isoelectric point 5.66. It shares 82.9% protein sequence homology with the ferritin of the Atlantic salmon. This gene is expressed in many organs of the Chinese sturgeon, for example, the liver, pancreas, muscle, brain, heart and gastric mucosa. The highest expression level was found in the pancreas and the heart, while the muscular tissue showed the lowest. Homology modeling was used to predict the 3-D structure of the protein, which included 5 alpha helices and 10 turns. The ferritin protein structure could be overlapped and showed high similarity with that of human, flog and bacteria. It was revealed that this kind of ferritin was highly conserved in structure and function.
基金the National Natural Science Foundation of China:Mechanism of Acupuncture in Extending Thrombolytic Time Window of Cerebral Infarction Based on Nuclear Receptor Coactivator 4 Mediated Ferritinophagy(No.82205238)National Natural Science Foundation of China:Exploring the Mechanism of Acupuncture Improving Thrombolytic Safety in Cerebral Infarction through the ERK1/2-mTOR Pathway Based on Autophagy Apoptosis Interaction(No.82074525)+1 种基金Natural Science Foundation of Jiangsu Province:Experimental Study on Acupuncture Regulation of Ferroptosis-NLRP3 Inflammasome Pathway to Reduce Hemorrhagic Transformation after Thrombolysis in Cerebral Infarction(No.BK20210689)Traditional Chinese Medicine Science and Technology Development Plan Project of Jiangsu Province:Clinical and Experimental Study on Acupuncture Improving the Safety of rt-PA Intravenous Thrombolysis in Cerebral Infarction(No.YB2020005)。
文摘OBJECTIVE:To explore the effect of acupuncture treatment on cerebral ischaemia-reperfusion injury(CIRI)and reveal the underlying mechanism of the effect based on nuclear receptor coactivator 4(NCOA4)mediated ferritinophagy.METHODS:Sprague-Dawley male rats were divided into four groups:the sham group,model group,acupuncture group,and sham acupuncture group.After 2 h of middle cerebral artery occlusion(MCAO),reperfusion was performed for 24 h to induce CIRI.The rats were treated with acupuncture at the Neiguan(PC6)and Shuigou(GV26)acupoints.Their neurological function was evaluated by taking their Bederson scores at 2 h after ischaemia and 24 h after reperfusion.Triphenyltetrazolium chloride staining was applied to assess the cerebral infarct volume at 24 h after reperfusion.The malondialdehyde(MDA)and ferrous iron(Fe^(2+))levels were observed after 24 h of reperfusion using an assay kit.Western blotting was performed to detect the expression of NCOA4 and ferritin heavy chain 1(FTH1)at 24 h after reperfusion.Moreover,the colocalization of ferritin with neurons,NCOA4 with microtubule-associated protein 1 light chain 3(LC3),and NCOA4 with ferritin was visualized using immunofluorescence staining.RESULTS:Acupuncture significantly improved neurological function and decreased cerebral infarct volume in the acupuncture group.Following CIRI,the expression of NCOA4,LC3 and FTH1 was increased,which enhanced ferritinophagy and induced an inappropriate accumulation of Fe^(2+)and MDA in the ischaemic brain.However,acupuncture dramatically downregulated the expression of NCOA4,LC3 and FTH1,inhibited the overactivation of ferritinophagy,and decreased the levels of MDA and Fe^(2+).CONCLUSIONS:Acupuncture can inhibit NCOA4-mediated ferritinophagy and protect neurons against CIRI in a rat model.
文摘Animal cells require extrinsic cues for growth, proliferation and survival. The propagation of Drosophila imaginal disc cells in vitro, for example, requires the supplementation of fly extract, the composition of which remains largely undefined. Here I report the biochemical purification of iron-loaded ferritin as an active ingredient of fly extract that is required for promoting the growth of clone 8 imaginal disc cells. Consistent with an essential role for iron- loaded ferritin in cultured cells, overexpression of ferritin or addition of iron in a nutrient-poor diet increases animal viability and body weight, promotes cell proliferation, and shortens the duration of postembryonic development. Conversely, overexpression of dominant-negative ferritin or addition of iron chelator causes the opposite effects. Fer- ritin mutant flies arrest development at the first-instar larval stage with a severe starvation phenotype reminiscent of that seen in starved larvae. I conclude that iron-loaded ferritin acts as an essential mitogen for cell proliferation and postembryonic development in Drosophila by maintaining iron homeostasis and antagonizing starvation response.
基金supported partially by the National Natural Science Foundation of China(Nos.62075118,21601112)the Natural Science Foundation of Shanxi Province(No.20210302123433)+2 种基金Key R&D program of Shanxi Province(International Cooperation,No.201903D421070,2021XM21)Shanxi Key Laboratory of Pharmaceutical Biotechnology(No.KF202003)Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(No.2019L0020)。
文摘Ferritins can generally be divided into four subfamilies based on their structural characteristics,namely,the classic ferritins(Ftns),bacterioferritins(Bfrs),DNA-binding proteins from starved cells(Dps’),and encapsulated ferritins(Enc Ftns).However,the ferritin from Mycoplasma penetrans(Mpef)possesses a particular ferroxidase center with an extreme low activity and exhibits unusual characteristics,indicating that it could be a member of a quite different subfamily of ferritins.Hereby,the crystal structure of the ferritin from Ureaplasma urealyticum(Uurf)is presented,Mpef and Uurf have very similar properties,though they display very low sequence similarity.Thus,ferritins from Mycoplasma with these unique properties do not belong to any known subfamily,but they should rather be placed in a novel ferritin subfamily,which we term Mycoplasma Ferritin(Mfr).
文摘目的初步探索Notch信号对树突状细胞(dendritic cell,DC)介导的抗寄生虫感染免疫反应的影响。方法体外培养骨髓来源的小鼠DC细胞,利用γ-分泌酶抑制剂N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine tbutyl ester,DAPT于不同时间段处理细胞,阻断DC的Notch信号通路,培养第7d时收集DC,用细粒棘球蚴重组抗原铁蛋白(ferritin protein of Echinococcus granulosus,Eg.ferritin)体外刺激DC,利用扫描电镜观察DC形态的改变,采用流式细胞术检测DC表面分子MHCⅡ、CD40及CD80/CD86的表达情况。结果 DC细胞数量随DAPT浓度的增高而降低;经不同浓度DAPT于不同时间段处理后,DC细胞中Notch1mRNA的表达受到抑制,以50μmol/L DAPT在第0d处理DC,对Notch1mRNA的抑制效果更显著(P<0.05);Eg.ferritin和LPS均能刺激DC细胞表面树突的生成及表面分子MHCⅡ、CD40及CD80/CD86的表达,且Eg.ferritin比LPS的刺激作用更显著(P<0.05),而加入DAPT后,DC细胞表面树突的生成减少,各表面分子的表达水平降低(P<0.05),并削弱了Eg.ferritin和LPS的刺激作用。结论Eg.ferritin能促进DC细胞的分化成熟,而阻断Notch信号通路会影响DC细胞的分化成熟,并降低DC细胞对Eg.ferritin的反应能力。其分子机制涉及Notch信号通路。
