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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： ning song,jun wang,hong jiang,jun-xia xie~* state key discipline:physiology(in incubation),department of physiology,qingdao university,qingdao,266071

＜正＞Objective Iron accumulation in the substantia nigra was thought to play an important role in the pathogenesis of Parkinson’s disease（PD）.Our in vivo experiments suggested that iron transporters ferroportinl（FP1） and hephaestin （HP） might account for the nigral iron accumulation in 6-hydroxydopamine（6-OHDA） lesioned PD *** present study is to explore the mechanisms underlying FP1 and HP mis-regulation in MES23.5 dopaminergic *** Realtime PCR and western blots were applied to detect FP1,HP,ferritin and iron regulatory protein（IRP） *** interfering RNA was applied for gene *** cytometry was applied to determine iron induced oxidative stress. Results Both FP1 and HP were down-regulated,followed by the decreased iron efflux in 6-OHDA treated MES23.5 cells. FP1 showed a dose-dependent up-regulation while HP showed no response in MES23.5 cells overloaded with ferric ammonium citrate,indicating that down-regulation of FP1 and HP was not due to the increased intracellular iron content. In 6-OHDA treated cells,both IRP1 and IRP2 were up-regulated,and silencing of IRPs in MES23.5 cells dramatically abolished 6-OHDA-induced FP1 down-regulation and even reversed HP *** of FP1 but not HP would lead to the intracellular iron accumulation in MES23.5 *** Down-regulations of both FP1 and HP by 6-OHDA were ***1 but not HP was involved in the 6-OHDA induced iron accumulation in MES23.5 cells.

关键词： ferroportinl hephaestin 6-hydroxydopamine iron Parkinson’s disease

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Ceruloplasmin is involved in the nigral iron accumulation of 6-OHDA lesioned rats

Ceruloplasmin is involved in the nigral iron accumulation of...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： jun wang hong jiang jun-xia xie~* state key discipline:physiology(in incubation) department of physiology qingdao university qingdao 266071

＜正＞Objective Elevated iron levels in the substantia nigra participate in neuronal death in Parkinson’s disease（PD）. While the mechanisms underlying the increased iron are still ***（CP） is a ferroxidase that converts highly toxic ferrous iron to its non-toxic ferric form,which cooperated with ferroportinl（FP1） facilitating the export of iron from reticuloendothelial system and other peripheral *** previous study showed that decreased expression of FP1 in the substantia nigra can account for the increased iron *** elucidate if the abnormal expression of CP is also involved in the nigral iron accumulation,here,we investigated CP expression in the substantia nigra of rats lesioned by 6- hydroxydopamine（6-OHDA）.Methods Immunofluorescence,immunohistochemistry and RT-PCR were used to observe the expression of ***（1） Using immunofluorescence,we showed mat FP1 and CP colocalized in the rat substantia nigra.（2） By immunohistochemistry,we observed that one day after 6-OHDA lesion,the expression of CP decreased compared with the *** rats began showing rotation behavior induced by apomorphine,usually after six weeks since 6-OHDA lesion,they are considered PD *** these PD models,a further decrease was observed.（3） RT-PCR showed that the mRNA level of CP decreased one day after 6-OHDA lesion compared with the control,and further decrease was also observed in the PD model *** These results show that FP1 and CP colocalize in the rat brain,indicating the coordinated actions of the two proteins in the iron export from neural cells;and suggest that decreased expression of CP in the substantia nigra is involved in the nigral iron accumulation of 6-OHDA lesioned rats.

关键词： 6-hydroxydopamine Ceruloplasmin iron Parkinson’s disease

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Protective effects of curcumin on 6-OHDA-induced Parkinson’s disease rat model

Protective effects of curcumin on 6-OHDA-induced Parkinson’...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Xi-Xun DU,jun wang,hong jiang,jun-xia xie~* state key discipline:physiology(in incubation),department of physiology,qingdao university,qingdao 266071, China

＜正＞Objective Curcumin is a well-defined *** has a neuroprotective effect due to its free radical scavenging, iron-chelating and anti-inflammatory actions in different *** the mechanism of its protective effects on dopaminergic neurons is still not *** HPLC-ECD was used to determine the content of DA and its metabolites:3,4- dihydroxyphenylacetic acid（DOPAC）,homovanillic acid（HVA） in striatum（Str）.Immunohistochemistry assay was used to detect the numbers of dopaminergic ***’s iron-staining to detect the iron levels in substantia nigra（SN）.Results （1） After 6-OHDA lesions,the DA and its metabolite DOPAC contents in the Str decreased compared with that of control, while the HVA level was not *** the curcumin treatment group,the DA and its metabolites contents increased compared with that of 6-OHDA treatment group.（2） The number of tyrosine hydroxylase（TH） positive neurons in the SN decreased after 6-OHDA lesions compared with that of control *** significantly inhibited 6-OHDA-induced decrease of the numbers of TH positive neurons.（3） The number of iron-staining cells increased in the SN decreased after 6-OHDA lesions compared with that of control *** significantly inhibited 6-OHDA-induced increase of the numbers of iron-staining *** Curcumin could significantly reduce the toxic effects of 6-OHDA on dopaminergic neurons in rat SN via its iron-chelating property.

关键词： curcumin Parkinson’s disease 6-hydroxydopamine iron

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Mysregulation of iron in Parkinson’s disease and its relation to the dopaminergic cell death

Mysregulation of iron in Parkinson’s disease and its relati...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： hong jiang,jun-xia xie~* state key discipline:physiology(in incubation),department of physiology,qingdao university

＜正＞Objective Iron plays a key role in Parkinson’s disease（PD） and elevated iron levels in the substantia nigra（SN） participate in neuronal death in *** the mechanisms underlying the increased iron are still unknown,some iron transport proteins may be *** nigral iron accumulation could be a result of either increased import or decreased *** investigated the role of iron import transporter divalent metal transporter 1（DMT1） and iron export transporter ferroportinl（FP1） in PD *** Expression of DMT1 and FP1 was identified by immunohistochemisty and western *** transfection,small interferring RNA and calcein-induced iron uptake were used to determine the funtion of DMT1 and *** We first observed DMT1 with the iron responsive element（ERE,DMT1+IRE） but not DMT1 without IRE（DMT 1-IRE） was up-regulated and FP1 down-regulated in vivo in the SN of 6-hydroxydopamine（6-OHDA）- induced PD rats,suggesting increased DMT1+IRE and decreased FP1 expression might account for the nigral iron accumulation in PD *** was father confirmed by our in vitro study in 6-OHDA-treated MES23.5 *** iron regulatory protein（IRP） 1 and IRP2 expression were observed,while silencing of IRPs dramatically diminished 6-OHDA-induced DMT1+IRE up-regulation and FP1 *** with N-acetyl-L-cysteine could fully suppress IRPs up-regulations by inhibiting 6-OHDA-induced oxidative *** Our data gave the direct evidence that DMT1+IRE up-regulation and FP1 down-regulation accounted for 6-OHDA-induced iron accumulation in an IRE/IRP-dependent manner,which was initiated by 6-OHDA-induced intracellular oxidative *** intracellular iron thus resulted in aggravated oxidative *** anti-oxidants,such as Rg1 and curcumin,showed neuroprotective effects. This study might support the use of anti-oxidants in the treatment of PD from a quite new angle,which could inhibit iron accumulation by regulating DMT1 and FP1 e

关键词： iron Parkinson’s disease divalent metal transporter 1 ferroportin 1 iron responsive element anti-oxidants

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Ghrelin protects MES23.5 cells against 1-Methyl-4-phenylpyridinium ioninduced cytotoxicity

Ghrelin protects MES23.5 cells against 1-Methyl-4-phenylpyri...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Li LIU,Hua-Min XU,hong jiang,jun wang,ning song,jun-xia xie~* state key disciplines:physiology(in incubation),department of physiology,qingdao university,qingdao 266071

Objective 1-Methyl-4-phenylpyridinium ion(MPP) has been widely used as a cellular model of Parkinson’s disease(PD),because it can elevate intracellular reactive oxygen species level and apoptotic death,eliciting a severe PD- like ***,a 28-amino acid peptide,is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R).Our previous data showed that ghrelin could protect dopaminergic neurons against 1 -methyl-4-phenyl-1,2,3,6- tetrahydropyridine(MPTP)-induced neurotoxicity in *** the present study,MPP-treated MES23.5 cells which could express GHS-R were used to further explore the underlying molecular mechanisms of this protective *** The MDA level was measured by MDA Assay ***-PCR and western-blots were adopted to detect the changes of catalase, SOD1,caspase-3 protein expression,and Bax/Bcl-2 ***(1) Ghrelin could suppress MPPMnduced lipid peroxidation in MES23.5 cells.(2) Ghrelin promoted the expression of endogenous antioxidant defense components including CAT and SOD 1.(3) Ghrelin could attenuate MPP-induced up-regulation of Bax/Bcl-2 ratio and the activation of *** Our results suggest that the protective effects of ghrelin on MPP-induced cytotoxicity may be ascribed to its anti-oxidative properties,anti-apoptotic activity via inducing expression of SOD1 and catalase,and regulation of Bcl-2 and Bax expression.

关键词： oxidative stress Parkinson’s disease ghrelin MPP+

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Iron transporters mis-regulation contributes to the nigral iron accumulation in Parkinson's disease

Iron transporters mis-regulation contributes to the nigral i...

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中国生理学会第十一届张锡钧基金全国青年优秀生理学学术论文交流及评奖会议

作者： ning song,hong jiang,jun wang,junxia xie (department of physiology,Shandong Provincial key Laboratory of Pathogenesis and Prevention of Neurological Disorders and state key disciplines:physiology,Medical College of qingdao university, qingdao,266071)

Iron plays a key role in Parkinson’s disease(PD).The reasons underlying the high iron content found in the substantia nigra(SN) of PD are largely *** observed in the SN of 6-hydroxydopamine(6-OHDA)-induced PD rats,ferroportinl(FPN1) and hephaestin(HP) were down-regulated,and divalent metal transporter 1 with the iron responsive element(IRE,DMT1+IRE) was up-regulated,suggesting these iron transporters misregulation might account for nigral iron

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Curcumin protects nigral dopaminergic neurons by iron-chelation in the 6-hydroxydopamine rat model of Parkinson's disease

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Neuroscience Bulletin 2012年第3期28卷 253-258页

作者： Xi-Xun Du Hua-Min Xu hong jiang ning song jun wang jun-xia xie department of physiology Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines:PhysiologyMedical College of Qingdao UniversityQingdao 266071China

Objective Curcumin is a plant polyphenolic compound and a major component of spice turmeric （Curcuma longa）. It has been reported to possess free radical-scavenging, iron-chelating, and anti-inflammatory properties in dif- ferent tissues. Our previous study showed that curcumin protects MES23.5 dopaminergic cells from 6-hydroxydopamine （6-OHDA）-induced neurotoxicity in vitro. The present study aimed to explore this neuroprotective effect in the 6-OHDA-lesioned rat model of Parkinson＇s disease in vivo. Methods Rats were given intragastric curcumin for 24 days. 6-OHDA lesioning was conducted on day 4 of curcumin treatment. Dopamine content was assessed by high-performance liquid chromatography with electrochemical detection, tyrosine hydroxylase （TH）-containing neurons by immunohistochemistry, and iron-containing cells by Perls＇ iron staining. Results The dopamine content in the striatum and the number of TH-immunoreactive neurons decreased after 6-OHDA treatment. Curcumin pretreatment reversed these changes. Further studies demonstrated that 6-OHDA treatment increased the number of iron-staining cells, which was dramatically decreased by curcumin pretreatment. Conclusion The protective effects of curcumin against 6-OHDA may be attributable to the ironchelating activity of curcumin to suppress the iron-induced degeneration of nigral dopaminergic neurons.

关键词： 6-hydroxydopamine curcumin Parkinson's disease dopaminergic neurons iron

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Nifedipine reduces iron overload-induced dopamine neuron degeneration by inhibition of iron accumulation in the substantia nigra of rats

Nifedipine reduces iron overload-induced dopamine neuron deg...

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中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： Ze-Gang MA,hong jiang,jun-xia xie~* department of physiology,Shandong Provincial key Laboratory of Pathogenesis and Prevention of Neurological Disorders and state key disciplines:physiology,Medical College of qingdao university,qingdao,266071

＜正＞The effects of nifedipine on iron overload-induced neurodegeneration in the substantia nigra（SN）-striatum system were *** high performance liquid chromatography-electrochemical detection（HPLC-ECD）,tyrosine hydroxylase（TH） immunohistochemistry and inductive coupled plasma emission spectrometer detection,we measured the dopamine neuron degeneration and iron content in the SN of rats overloaded with iron dextran,and assessed the effects of treatment with *** results showed that the dopamine content in the striatum decreased after iron dextran treatment,which could be restored by *** dextran overload increased iron content in the SN and reduced the numbers of TH-positive *** with nifedipine prevented the increase of iron content and restored the numbers of TH-positive neurons to control *** results suggested that the protective effects of nifedipine on the toxicity of iron-overload could be attributed to the nifedipine-suppressed iron toxicity.

关键词： Nifedipine Iron Dopamine neuron

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Alpha-synuclein aggregation is involved in the iron toxicity to SK-N-SH neuroblastoma cells

Alpha-synuclein aggregation is involved in the iron toxicity...

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中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： hong jiang~*,Qing HE,Wen-Jing LI,ning song,jun-xia xie~* department of physiology,Shandong Provincial key Laboratory of Pathogenesis and Prevention of Neurological Disorders and state key disciplines:physiology,Medical College of qingdao university,qingdao 266071,China

＜正＞Increased nigral iron levels and intracytoplasmic Lewy bodies（LBs） in the degenerating neurons are found in Parkinson’s disease（PD）.Whether LBs formation is involved in the toxicity of iron is largely *** the present study,the enhanced toxicity of alpha-synuclein aggregates was confirmed in cells with ferrous iron treatment and conversely,alpha-synuclein knockdown could exert protective effects against ferrous iron induced cell *** showed a novel study that down-regulation of nuclear factor E2-related factor 2（Nrf2） and heme oxygenase-1（HO-1） might contribute to iron-induced alpha-synuclein aggregation in SK-N-SH neuroblastoma *** iron induced time-course regulation of Nrf2 and *** high ferrous iron conditions,alpha-synuclein over-expression led to more greatly down-regulation of Nrf2 and HO-1 levels,accompanied by more alpha-synuclein aggragates,while alpha-synuclein knockdown brought Nrf2 and HO-1 to the basal levels in cells with almost none alpha-synuclein *** further demonstrated that increased HO-1 expression could promote alpha-synuclein mRNA *** also showed that the predicated iron responsive element（IRE） in the 5’-UTR of alpha-synuclein is a functional *** is probably important for the post-transcriptional regulation of *** these together,our results provide a novel pathway that ferrous iron induces alpha-synuclein aggregation and exerts neurotoxicity by inhibiting Nrf2/ HO-1 and IRP-IRE binding,proposing a vicious cycle of iron accumulation,alpha-synuclein aggregation and HO-1 disturbance in PD.

关键词： Parkinson’s disease Lewy body alpha-synuclein iron iron responsive element

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Activation of ATP-sensitive potassium channels enhances DMT1mediated ferrous iron uptake in SK-N-SH cells

Activation of ATP-sensitive potassium channels enhances DMT1...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Xi-Xun DU,Hua-Min XU,ning song,hong jiang,jun-xia xie~* department of physiology,Shandong Provincial key Laboratory of Pathogenesis and Prevention of Neurological Disorders and state key disciplines:physiology,Medical College of qingdao university,qingdao 266071,China

Objective Elevated iron accumulation has been reported in the substantia nigra(SN) in Parkinson’s disease(PD).Our previous study observed that increased levels of the iron importer divalent metal transporter 1(DMTl) were involved in this nigral iron accumulation and dopaminergic neurons loss in *** iron transport function of DMTl is also related to the membrane potential level,which increases with hyperpolarization of the cell membrane. Activation of ATP-sensitive potassium(K) channels,which could induce hyperpolarization of nigral dopaminergic neurons,is reported to be involved in the selective loss of these neurons in *** present study is to investigate whether activation of K channels could change the iron uptake function of *** DiBAC4(3) and calcein were used to detect membrane potential and ferrous iron *** iron concentration was measured using an inductively coupled plasma(ICP-2) *** transmembrane potential(△Ψm) and reactive oxygen species(ROS) were measured by flow cytometry using rhodamine123 and ***(1) When treated with diazoxide,a novel K channel opener,the membrane potential of SK-N-SH cells showed hyperpolarization.(2) The influx of ferrous iron and the intracellular iron levels were observed dramatically increased When the cells were co-incubated with diazoxide and ferrous iron,resulting in a decreased△Ψm and an elevated level of ROS production.(3) When treated with diazoxide,cells overexpressing SUR1 and Kir6.2 showed increased ferrous iron influx compared with the vector control,which induced a decrease in△Ψm and an increase in ROS production. Conclusion These results suggest that the activation of the K channels could enhance DMT 1-mediated ferrous iron uptake,leading to increase intracellular oxidative stress.

关键词： divalent metal transporter 1 iron ATP-sensitive potassium Parkinson’s disease

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