Molecular Probes Shed Light on Magnesium Homeostasis

项目总结 镁水平调节参与糖酵解、克雷布斯循环和呼吸的酶的活性。 保守链；因此有可能影响增加细胞寿命所需的代谢转化- 癌症的侵袭性和侵袭性。然而，镁的动态平衡在癌症中的作用仍然不是很清楚。 主要是由于缺乏有效的工具来无干扰地检测细胞中的镁离子 从其他生物相关的金属中分离出来。例如，前列腺积聚了大量的二价体。 作为前列腺液的一部分，与柠檬酸盐一起分泌的阳离子，如镁、锌和钙。 需要正常的腺体功能。金属动态平衡的破坏被认为与 在从柠檬酸生产到柠檬酸氧化的代谢转变中，在去肿瘤阶段之前。 前列腺癌的发展。鉴于在阐明其他基因的作用方面已经取得了很大进展 在这一过程中，镁在前列腺癌病因中的作用仍然是一个谜。在……里面 在这项建议中，我们试图优化用于镁的选择性可视化和定量的分子探针 在含有高水平干扰金属的样品中，并利用新的工具来建立 前列腺细胞和组织中镁的蓄积与代谢活动和疾病进展的关系 太夸张了。这些研究代表着朝着获得金属组学的完整图像迈出的关键的第一步 以及建立镁离子在代谢重编程相关中的可能作用。 埃德得了癌症。该项目的具体目标包括：(I)开发用于可视化的最佳分子探针 以及对干扰金属含量高的组织中细胞内镁离子的定量；(Ii)绘制分布图 代表前列腺癌不同阶段的前列腺组织样品中的镁和其他二价金属阳离子 研究肿瘤细胞摄取镁离子与代谢活性的关系 细胞。这些研究将为镁作为一种新的、迄今未被探索的影响因素的作用提供新的见解 代谢转化发生在前列腺癌的早期阶段。对这种联系的更深层次的理解是- 镁稳态与癌症进展之间的关系可能会导致新的治疗焦油的发现。 集中在阳离子运输上，并打开了将金属水平用作生物标志物的大门- 为前列腺癌和其他癌症开发新的诊断和监测工具。

PROJECT SUMMARY Magnesium levels modulate the activity of enzymes involved in glycolysis, the Krebs cycle, and the respira- tory chain; thus have the potential to influence the metabolic transformation required for increased cell prolifer- ation and invasiveness in cancer. The role of magnesium homeostasis in cancer, however, has remained un- derexplored, mainly due to the paucity of efficient tools for the detection of Mg2+ in cells without interference from other biologically–relevant metals. For example, the prostate gland accumulates high levels of divalent cations such as Mg2+, Zn2+ and Ca2+, which are secreted with citrate as part of the prostatic fluid and are re- quired for proper gland function. Disruption of metal homeostasis has been proposed to be intimately involved in the metabolic shift from citrate production to citrate oxidation that precedes the neoplastic stage in the de- velopment of prostate malignancies. Whereas much progress has been made on elucidating the role of other divalent cations in this process, the role of magnesium in the etiology of prostate cancer is still a mystery. In this proposal, we seek to optimize molecular probes for selective visualization and quantification of magnesium in samples with high levels of interfering metals, and to capitalize on the new tools to establish the patterns of magnesium accumulation in prostate cells and tissue in relationship with metabolic activity and disease pro- gression. These studies represent a critical first step toward obtaining a complete picture of the metallome of the prostate gland and establishing the possible role of Mg2+ cations in the metabolic reprogramming associat- ed with cancer. The specific aims of the project include (i) to develop optimal molecular probes for visualization and quantification of intracellular Mg2+ in tissues with high levels of interfering metals; (ii) to map the distribution of Mg2+ and other divalent metal cations in prostate tissue samples representative of different stages of pros- tate malignancy; and (iii) to study the correlation between cellular Mg2+ uptake with metabolic activity in cancer cells. These studies will offer new insight into the role of Mg2+ as a new, thus far unexplored factor influencing the metabolic transformation occurring in early stages of PCa. Deeper understanding of the connection be- tween magnesium homeostasis and cancer progression may lead to the identification of new therapeutic tar- gets centered in cation transport, and open the door to the use of metal levels as biomarkers for the develop- ment of novel diagnostic and surveillance tools for PCa and other cancers.