硝普鈉對(duì)SH-SY5Y細(xì)胞中F-box富含亮氨酸重復(fù)蛋白5和鐵調(diào)節(jié)蛋白2表達(dá)的調(diào)節(jié)作用（英文）
發(fā)布時(shí)間：2018-11-24 20:24
【摘要】：帕金森病(Parkinson’s disease,PD)患者早期鐵選擇性聚集在黑質(zhì)致密帶,殘存的多巴胺能神經(jīng)元內(nèi)鐵含量增高,說明鐵升高可能是PD發(fā)生的一個(gè)關(guān)鍵因素。鐵調(diào)節(jié)蛋白(iron regulatory proteins,IRPs)IRP1和IRP2可與鐵轉(zhuǎn)運(yùn)和儲(chǔ)存蛋白中的鐵反應(yīng)元件相結(jié)合,對(duì)維持細(xì)胞鐵穩(wěn)態(tài)起重要作用。F-box富含亮氨酸重復(fù)蛋白5(F-box and leucine-rich repeat protein 5,FBXL5)通過泛素蛋白酶體途徑降解IRP2而參與鐵代謝的調(diào)控。有研究顯示一氧化氮(nitric oxide,NO)能夠增強(qiáng)IRP1的活性,但對(duì)IRP2的表達(dá)影響尚未明確。本研究選擇NO的供體硝普納(sodium nitroprusside,SNP)作為處理藥物,研究其對(duì)體外培養(yǎng)的SH-SY5Y細(xì)胞內(nèi)FBXL5和IRP2蛋白表達(dá)的影響。細(xì)胞活力檢測(cè)結(jié)果顯示SNP可劑量依賴性地?fù)p傷SH-SY5Y細(xì)胞,降低細(xì)胞存活率。流式細(xì)胞術(shù)結(jié)果顯示,經(jīng)過100和300μmol/L的SNP處理后,細(xì)胞線粒體膜電位分別降低45%和60%。此外,Western blotting結(jié)果顯示300μmol/L SNP能夠引起細(xì)胞內(nèi)FBXL5的蛋白表達(dá)量升高39%,而使IRP2的蛋白表達(dá)量降低46%。以上結(jié)果提示,SNP可造成SH-SY5Y細(xì)胞的線粒體功能障礙,并上調(diào)FBXL5的表達(dá)和下調(diào)IRP2的表達(dá)。
[Abstract]:In the early stage of Parkinson's disease (Parkinson's disease,PD), iron selectively accumulates in the substantia nigra compact zone, and the iron content in the remaining dopaminergic neurons increases, suggesting that the increase of iron may be a key factor in the occurrence of PD. Iron regulatory proteins (iron regulatory proteins,IRPs) IRP1 and IRP2 can bind to iron reactive elements in iron transport and storage proteins and play an important role in maintaining iron homeostasis in cells. FBXL5) participates in the regulation of iron metabolism through the degradation of IRP2 by ubiquitin proteasome pathway. Some studies have shown that nitric oxide (nitric oxide,NO) can enhance the activity of IRP1, but the effect on the expression of IRP2 is not clear. In this study, the donor of NO (sodium nitroprusside,SNP) was selected as the treatment drug to study the effect of sodium nitroprusside,SNP on the expression of FBXL5 and IRP2 protein in cultured SH-SY5Y cells. The results of cell viability test showed that SNP could damage SH-SY5Y cells in a dose-dependent manner and reduce cell viability. Flow cytometry showed that after 100 渭 mol/L and 300 渭 mol/L SNP treatment, the mitochondrial membrane potential of the cells decreased by 45% and 60, respectively. In addition, Western blotting results showed that 300 渭 mol/L SNP could increase the protein expression of FBXL5 and decrease the protein expression of IRP2 by 39% and 46% respectively. These results suggest that SNP can induce mitochondrial dysfunction in SH-SY5Y cells and up-regulate the expression of FBXL5 and down-regulate the expression of IRP2.
【作者單位】： 青島大學(xué)醫(yī)學(xué)院生理學(xué)教研室山東省神經(jīng)相關(guān)疾病重點(diǎn)實(shí)驗(yàn)室山東省神經(jīng)退變疾病協(xié)同創(chuàng)新中心;
【基金】：supported by the National Natural Science Foundation of China(No.31471114,31500837 and 31540075) Taishan Scholarship,the Key Research and Development Program of Shandong Province,China(No.2016GSF201053) Qingdao Municipal Science and Technology Project(No.16-6-2-2-nsh) the Shandong Provincial Natural Science Foundation of China(No.BS2015SW022)
【分類號(hào)】：R742.5
本文編號(hào)：2354927
[Abstract]:In the early stage of Parkinson's disease (Parkinson's disease,PD), iron selectively accumulates in the substantia nigra compact zone, and the iron content in the remaining dopaminergic neurons increases, suggesting that the increase of iron may be a key factor in the occurrence of PD. Iron regulatory proteins (iron regulatory proteins,IRPs) IRP1 and IRP2 can bind to iron reactive elements in iron transport and storage proteins and play an important role in maintaining iron homeostasis in cells. FBXL5) participates in the regulation of iron metabolism through the degradation of IRP2 by ubiquitin proteasome pathway. Some studies have shown that nitric oxide (nitric oxide,NO) can enhance the activity of IRP1, but the effect on the expression of IRP2 is not clear. In this study, the donor of NO (sodium nitroprusside,SNP) was selected as the treatment drug to study the effect of sodium nitroprusside,SNP on the expression of FBXL5 and IRP2 protein in cultured SH-SY5Y cells. The results of cell viability test showed that SNP could damage SH-SY5Y cells in a dose-dependent manner and reduce cell viability. Flow cytometry showed that after 100 渭 mol/L and 300 渭 mol/L SNP treatment, the mitochondrial membrane potential of the cells decreased by 45% and 60, respectively. In addition, Western blotting results showed that 300 渭 mol/L SNP could increase the protein expression of FBXL5 and decrease the protein expression of IRP2 by 39% and 46% respectively. These results suggest that SNP can induce mitochondrial dysfunction in SH-SY5Y cells and up-regulate the expression of FBXL5 and down-regulate the expression of IRP2.
【作者單位】： 青島大學(xué)醫(yī)學(xué)院生理學(xué)教研室山東省神經(jīng)相關(guān)疾病重點(diǎn)實(shí)驗(yàn)室山東省神經(jīng)退變疾病協(xié)同創(chuàng)新中心;
【基金】：supported by the National Natural Science Foundation of China(No.31471114,31500837 and 31540075) Taishan Scholarship,the Key Research and Development Program of Shandong Province,China(No.2016GSF201053) Qingdao Municipal Science and Technology Project(No.16-6-2-2-nsh) the Shandong Provincial Natural Science Foundation of China(No.BS2015SW022)
【分類號(hào)】：R742.5
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