Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, 8 Lavrentiev Ave., Novosibirsk 630090, Russia.
J Mol Recognit. 2013 Jan;26(1):10-22. doi: 10.1002/jmr.2217.
Cobalt is a transition metal and an essential trace element that is required for vitamin B₁₂ biosynthesis, enzyme activation, and so on but is toxic in high concentrations. It was shown that the content of different elements in the plasma of 2-month-old BALB/c mice (control group) decreased in the following order: Ca > Mg > Si > Fe > Zn > Cu ≥ Al ≥ B. The treatment of mice with CoCl₂ did not appreciably change the relative content of Ca, Cu, and Zn, but a significant increase in the content of B (2.3-fold), Mg (1.5-fold), Al and Fe (2.1-fold), and Si (3.4-fold) was found. The treatment of mice led to a 2.2-fold decrease in the concentration of the total blood protein and a 1.7 ± 0.2-fold decrease of total immunoglobulin Gs (IgGs). Deoxyribonuclease IgGs corresponding to mice treated (t-IgGs) and non-treated (nt-IgGs) with CoCl₂ contained intrinsically bound metal ions; these IgGs hydrolyzed DNA with very low activity but were not active in the presence of ethylenediaminetetraacetic acid or after Ab dialysis against ethylenediaminetetraacetic acid. The average RAs of deoxyribonuclease nt-IgGs increased after addition of external metal ions in the following order: Zn²⁺< Ca²⁺ < Cu²⁺ < Fe²⁺ < Mn²⁺ < Mg²⁺ < Co²⁺ < Ni²⁺. Interestingly, t-IgGs demonstrated lower activities than those for nt-IgGs either in the absence of external metal ions (2.7-fold) or in the presence of Cu²⁺ (9.5-fold) > Co²⁺ (5.6-fold) > Zn²⁺ (5.1-fold) > Mg²⁺ (4.1-fold) > Ca²⁺ (3.0-fold) > Fe²⁺ (1.3-fold). However, the RAs of t-IgGs were remarkably more active than nt-IgGs in the presence of best activators of t-IgGs Ni²⁺ (1.4-fold) and especially Mn²⁺ (2.2-fold). The data may be useful for an understanding of Co toxicity, its effect on the concentration of other metal ions, and a change of metal-dependent specificity of Abzs.
钴是一种过渡金属和必需的微量元素,它是维生素 B₁₂生物合成、酶激活等所必需的,但在高浓度下是有毒的。研究表明,2 个月大的 BALB/c 小鼠(对照组)血浆中不同元素的含量按以下顺序降低:Ca>Mg>Si>Fe>Zn>Cu≥Al≥B。用 CoCl₂处理小鼠不会显著改变 Ca、Cu 和 Zn 的相对含量,但会显著增加 B(2.3 倍)、Mg(1.5 倍)、Al 和 Fe(2.1 倍)和 Si(3.4 倍)的含量。用 CoCl₂处理小鼠导致总血蛋白浓度降低 2.2 倍,总免疫球蛋白 G(IgG)降低 1.7±0.2 倍。用 CoCl₂处理(t-IgGs)和未处理(nt-IgGs)的小鼠的脱氧核糖核酸酶 IgG 含有内在结合的金属离子;这些 IgG 对 DNA 的水解活性非常低,但在乙二胺四乙酸存在或在用乙二胺四乙酸进行 Ab 透析后没有活性。添加外源金属离子后,脱氧核糖核酸酶 nt-IgGs 的平均 RA 按以下顺序增加:Zn²⁺<Ca²⁺<Cu²⁺<Fe²⁺<Mn²⁺<Mg²⁺<Co²⁺<Ni²⁺。有趣的是,t-IgGs 无论是在没有外源金属离子的情况下(2.7 倍)还是在存在 Cu²⁺(9.5 倍)>Co²⁺(5.6 倍)>Zn²⁺(5.1 倍)>Mg²⁺(4.1 倍)>Ca²⁺(3.0 倍)>Fe²⁺(1.3 倍)的情况下,其活性均低于 nt-IgGs。然而,在 t-IgGs 的最佳激活剂 Ni²⁺(1.4 倍)和 Mn²⁺(2.2 倍)的存在下,t-IgGs 的 RA 明显高于 nt-IgGs。这些数据可能有助于理解 Co 的毒性、它对其他金属离子浓度的影响以及 Abzs 的金属依赖性特异性的变化。