{"title":"在猪脑毛细血管内皮细胞培养模型系统中,锌调控铜在血脑屏障上的双向转移。","authors":"Denny Pellowski , Franziska Ebert , Julia Bornhorst , Tanja Schwerdtle","doi":"10.1016/j.jtemb.2024.127547","DOIUrl":null,"url":null,"abstract":"<div><div>The blood-brain barrier (BBB) serves as a crucial interface, regulating the transfer of trace elements (TEs) such as copper (Cu) and zinc (Zn) between the bloodstream and the brain. Cu and Zn are essential for maintaining neural function and enzymatic processes. Understanding the interplay of Cu and Zn with the BBB is crucial for elucidating their roles in neurological health and disease. This study investigates the bidirectional transfer of Cu across the BBB and examines the impact of Zn supplementation on this process using a porcine brain capillary endothelial cell (PBCEC) model. Transendothelial electrical resistance (TEER) and capacitance measurements confirmed barrier integrity upon TE exposure, while quantification of Cu and Zn concentrations <em>via</em> inductively coupled plasma-tandem mass spectrometry (ICP-MS/MS) in the culture medium provided essential baseline data. Transfer studies revealed significant increases in basolateral (brain side) Cu concentrations after apical (blood side) Cu incubation, with additional Zn supplementation reducing Cu transfer from apical to basolateral compartments. Conversely, Zn incubation showed no effect on basolateral-to-apical Cu transfer. Surprisingly, it was found that Cu also transferred significantly to the apical compartments when incubated basolaterally, and with slightly higher permeability coefficients than <em>vice versa</em>, indicating a potential role of PBCECs in regulating Cu transport both from blood to brain and from brain to blood. These findings suggest a bidirectional Cu trafficking across PBCECs, only slightly influenced unidirectionally by Zn supplementation, highlighting the intricate interplay between TEs at the BBB. Importantly, no alterations in barrier integrity were observed, underscoring the physiological relevance of the experimental conditions. Overall, this study sheds light on the complex dynamics of Cu and Zn transfer at the BBB, emphasizing the need for comprehensive investigations into TE interactions for a deeper understanding of brain TE homeostasis.</div></div>","PeriodicalId":49970,"journal":{"name":"Journal of Trace Elements in Medicine and Biology","volume":"86 ","pages":"Article 127547"},"PeriodicalIF":3.6000,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Zinc-modulated bidirectional copper transfer across the blood-brain barrier in a porcine brain capillary endothelial cell culture model system\",\"authors\":\"Denny Pellowski , Franziska Ebert , Julia Bornhorst , Tanja Schwerdtle\",\"doi\":\"10.1016/j.jtemb.2024.127547\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>The blood-brain barrier (BBB) serves as a crucial interface, regulating the transfer of trace elements (TEs) such as copper (Cu) and zinc (Zn) between the bloodstream and the brain. Cu and Zn are essential for maintaining neural function and enzymatic processes. Understanding the interplay of Cu and Zn with the BBB is crucial for elucidating their roles in neurological health and disease. This study investigates the bidirectional transfer of Cu across the BBB and examines the impact of Zn supplementation on this process using a porcine brain capillary endothelial cell (PBCEC) model. Transendothelial electrical resistance (TEER) and capacitance measurements confirmed barrier integrity upon TE exposure, while quantification of Cu and Zn concentrations <em>via</em> inductively coupled plasma-tandem mass spectrometry (ICP-MS/MS) in the culture medium provided essential baseline data. Transfer studies revealed significant increases in basolateral (brain side) Cu concentrations after apical (blood side) Cu incubation, with additional Zn supplementation reducing Cu transfer from apical to basolateral compartments. Conversely, Zn incubation showed no effect on basolateral-to-apical Cu transfer. Surprisingly, it was found that Cu also transferred significantly to the apical compartments when incubated basolaterally, and with slightly higher permeability coefficients than <em>vice versa</em>, indicating a potential role of PBCECs in regulating Cu transport both from blood to brain and from brain to blood. These findings suggest a bidirectional Cu trafficking across PBCECs, only slightly influenced unidirectionally by Zn supplementation, highlighting the intricate interplay between TEs at the BBB. Importantly, no alterations in barrier integrity were observed, underscoring the physiological relevance of the experimental conditions. Overall, this study sheds light on the complex dynamics of Cu and Zn transfer at the BBB, emphasizing the need for comprehensive investigations into TE interactions for a deeper understanding of brain TE homeostasis.</div></div>\",\"PeriodicalId\":49970,\"journal\":{\"name\":\"Journal of Trace Elements in Medicine and Biology\",\"volume\":\"86 \",\"pages\":\"Article 127547\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-10-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Trace Elements in Medicine and Biology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0946672X24001676\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Trace Elements in Medicine and Biology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0946672X24001676","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
血脑屏障(BBB)是一个重要的界面,它调节着铜(Cu)和锌(Zn)等微量元素(TE)在血液和大脑之间的转移。铜和锌对维持神经功能和酶过程至关重要。了解铜和锌与 BBB 的相互作用对于阐明它们在神经系统健康和疾病中的作用至关重要。本研究利用猪脑毛细血管内皮细胞(PBCEC)模型研究了铜在 BBB 上的双向转移,并探讨了补充锌对这一过程的影响。经内皮电阻(TEER)和电容测量证实了暴露于 TE 时屏障的完整性,而通过电感耦合等离子体串联质谱法(ICP-MS/MS)对培养基中的铜和锌浓度进行定量则提供了重要的基线数据。转移研究显示,顶端(血液侧)铜培养后,基底侧(大脑侧)铜浓度明显增加,额外的锌补充减少了铜从顶端向基底侧的转移。相反,锌孵育对基底侧到顶端的铜转移没有影响。令人惊讶的是,研究发现,当铜在基底侧培养时,也会显著转移到顶端区室,而且渗透系数略高于基底侧培养,这表明 PBCECs 在调节铜从血液到大脑以及从大脑到血液的转运中发挥了潜在作用。这些研究结果表明,铜在 PBCECs 上的运输是双向的,而单向运输只受到锌补充的轻微影响,这突显了 BBB 中 TEs 之间错综复杂的相互作用。重要的是,没有观察到屏障完整性的改变,这强调了实验条件的生理相关性。总之,这项研究揭示了铜和锌在 BBB 转移的复杂动态,强调了全面研究 TE 相互作用的必要性,以加深对脑 TE 平衡的理解。
Zinc-modulated bidirectional copper transfer across the blood-brain barrier in a porcine brain capillary endothelial cell culture model system
The blood-brain barrier (BBB) serves as a crucial interface, regulating the transfer of trace elements (TEs) such as copper (Cu) and zinc (Zn) between the bloodstream and the brain. Cu and Zn are essential for maintaining neural function and enzymatic processes. Understanding the interplay of Cu and Zn with the BBB is crucial for elucidating their roles in neurological health and disease. This study investigates the bidirectional transfer of Cu across the BBB and examines the impact of Zn supplementation on this process using a porcine brain capillary endothelial cell (PBCEC) model. Transendothelial electrical resistance (TEER) and capacitance measurements confirmed barrier integrity upon TE exposure, while quantification of Cu and Zn concentrations via inductively coupled plasma-tandem mass spectrometry (ICP-MS/MS) in the culture medium provided essential baseline data. Transfer studies revealed significant increases in basolateral (brain side) Cu concentrations after apical (blood side) Cu incubation, with additional Zn supplementation reducing Cu transfer from apical to basolateral compartments. Conversely, Zn incubation showed no effect on basolateral-to-apical Cu transfer. Surprisingly, it was found that Cu also transferred significantly to the apical compartments when incubated basolaterally, and with slightly higher permeability coefficients than vice versa, indicating a potential role of PBCECs in regulating Cu transport both from blood to brain and from brain to blood. These findings suggest a bidirectional Cu trafficking across PBCECs, only slightly influenced unidirectionally by Zn supplementation, highlighting the intricate interplay between TEs at the BBB. Importantly, no alterations in barrier integrity were observed, underscoring the physiological relevance of the experimental conditions. Overall, this study sheds light on the complex dynamics of Cu and Zn transfer at the BBB, emphasizing the need for comprehensive investigations into TE interactions for a deeper understanding of brain TE homeostasis.
期刊介绍:
The journal provides the reader with a thorough description of theoretical and applied aspects of trace elements in medicine and biology and is devoted to the advancement of scientific knowledge about trace elements and trace element species. Trace elements play essential roles in the maintenance of physiological processes. During the last decades there has been a great deal of scientific investigation about the function and binding of trace elements. The Journal of Trace Elements in Medicine and Biology focuses on the description and dissemination of scientific results concerning the role of trace elements with respect to their mode of action in health and disease and nutritional importance. Progress in the knowledge of the biological role of trace elements depends, however, on advances in trace elements chemistry. Thus the Journal of Trace Elements in Medicine and Biology will include only those papers that base their results on proven analytical methods.
Also, we only publish those articles in which the quality assurance regarding the execution of experiments and achievement of results is guaranteed.