JBIC Journal of Biological Inorganic Chemistry ( IF 2.7 ) Pub Date : 2021-07-24 , DOI: 10.1007/s00775-021-01883-7 Karina Sayuri Utsunomiya 1 , Lucas Jonatas da Silva 1 , Juliana Iwamoto 1 , Rodrigo Polimeni Constantin 1 , Eduardo Hideo Gilglioni 1 , Jorgete Constantin 1 , Adelar Bracht 1 , Ronald Petrus Johannes Oude Elferink 2 , Emy Luiza Ishii-Iwamoto 1
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In the present work, the multiple-indicator dilution (MID) technique was used to investigate the kinetic mechanisms by which nickel (Ni2+) affects the calcium (Ca2+) transport in intact rat liver. 45Ca2+ and extra- and intracellular space indicators were injected in livers perfused with 1 mM Ni2+, and the outflow profiles were analyzed by a mathematical model. For comparative purposes, the effects of norepinephrine were measured. The influence of Ni2+ on the cytosolic Ca2+ concentration ([Ca2+]c) in human hepatoma Huh7 cells and on liver glycogen catabolism, a biological response sensitive to cellular Ca2+, was also evaluated. The estimated transfer coefficients of 45Ca2+ transport indicated two mechanisms by which Ni2+ increases the [Ca2+]c in liver under steady-state conditions: (1) an increase in the net efflux of Ca2+ from intracellular Ca2+ stores due to a stimulus of Ca2+ efflux to the cytosolic space along with a diminution of Ca2+ re-entry into the cellular Ca2+ stores; (2) a decrease in Ca2+ efflux from the cytosolic space to vascular space, minimizing Ca2+ loss. Glycogen catabolism activated by Ni2+ was transient contrasting with the sustained activation induced by norepinephrine. Ni2+ caused a partial reduction in the norepinephrine-induced stimulation in the [Ca2+]c in Huh7 cells. Our data revealed that the kinetic parameters of Ca2+ transport modified by Ni2+ in intact liver are similar to those modified by norepinephrine in its first minutes of action, but the membrane receptors or Ca2+ transporters affected by Ni2+ seem to be distinct from those known to be modulated by norepinephrine.
Graphic abstract
中文翻译：
镍改变完整大鼠肝脏中钙 (Ca2+) 转运的动力学机制
在目前的工作中，多指标稀释 (MID) 技术用于研究镍 (Ni 2+ ) 影响完整大鼠肝脏中钙 (Ca 2+ ) 转运的动力学机制。将45 Ca 2+和细胞内外空间指示剂注射到灌注有1 mM Ni 2+ 的肝脏中，并通过数学模型分析流出曲线。出于比较的目的，测量了去甲肾上腺素的作用。Ni 2+对人肝癌 Huh7 细胞中细胞溶质 Ca 2+浓度（[Ca 2+ ] c）和肝糖原分解代谢的影响，这是一种对细胞 Ca 敏感的生物反应2+，也被评估。45 Ca 2+转运的估计转移系数表明在稳态条件下Ni 2+增加肝脏中[Ca 2+ ] c 的两种机制：（1）Ca 2+从细胞内Ca的净流出增加2+由于钙刺激存储2+流出到用Ca的减少沿胞质腔2+重新进入细胞的Ca 2+存储; (2)从胞质间隙到血管间隙的Ca 2+流出减少，使 Ca 2+损失最小化。Ni激活糖原分解代谢2+是短暂的，与去甲肾上腺素诱导的持续激活形成对比。Ni 2+导致去甲肾上腺素诱导的Huh7 细胞[Ca 2+ ] c刺激部分减少。我们的数据显示，完整肝脏中由 Ni 2+修饰的 Ca 2+转运的动力学参数与去甲肾上腺素在其作用的最初几分钟内修饰的动力学参数相似，但受 Ni 2+影响的膜受体或 Ca 2+转运蛋白似乎与已知受去甲肾上腺素调节的那些不同。
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