EFFECTS OF INORGANIC AND ORGANIC MERCURY ON INTRACELLULAR CALCIUM LEVELS IN RAT LYMPHOCYTES-T
EFFECTS OF INORGANIC AND ORGANIC MERCURY ON INTRACELLULAR CALCIUM LEVELS IN RAT LYMPHOCYTES-T
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DOI：
10.1080/15287399309531709
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发表时间：
1993-02-01
期刊：
影响因子：
--
通讯作者：
COSTA, LG
中科院分区：
文献类型：
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作者：
TAN, XX;TANG, C;COSTA, LG
细胞内游离钙离子水平（[Ca 2 +]i）在淋巴细胞活化中的重要性促使我们研究汞化合物引起的T细胞[Ca 2 +]i的变化，汞化合物已被证明具有免疫调节和免疫毒性特性。用Fura-2作Ca ~（2+）荧光指示剂，发现甲基汞（MeHg; 0.02-2 μ M）和无机汞（HgCl_2; 0.01-1 μ M）均能使大鼠脾淋巴细胞内[Ca ~（2+）]i浓度依赖性增加。MeHg作用迅速，Ca 2+升高持续时间较长，HgCl 2引起[Ca 2 +]i缓慢升高。汞化合物的影响似乎并不与膜完整性的改变，因为有没有显着差异，在控制和汞处理的细胞之间的氯化锰淬火的程度。然而，氯化汞（1 μ M）和甲基汞（2 μ M）出现在较长的孵育时间（15分钟）造成膜损伤。当细胞在无Ca 2+的培养基中孵育时（在存在1 mM EDTA的情况下），甲基汞仍然增加[Ca 2 +]i，尽管程度较小，而HgCl 2则没有影响。肝素，肌醇1，4，5，-三磷酸诱导的Ca 2+动员的抑制剂，部分地阻止了[Ca 2 +]i的这种上升，而羰基氰间氯苯腙（CCCP），线粒体功能的抑制剂，有较小的影响。当肝素和CCCP加在一起时，几乎完全阻断了对甲基汞的反应。这些结果表明，甲基汞和氯化汞发挥其影响的[Ca 2 +]i在不同的方式：甲基汞诱导的增加[Ca 2 +]i是由于流入细胞外，以及从细胞内的存储，可能的内质网，并在较小的程度上，线粒体的动员;另一方面，氯化汞导致只有Ca 2+流入细胞外介质。
The importance of cytosolic free calcium level ([Ca2+]i) in lymphocyte activation prompted us to investigate changes in [Ca2+]i in T cells caused by mercury compounds, which have been shown to have immunomodulatory and immunotoxic properties. Using fura-2 as fluorescent Ca2+ indicator we found that both methyl-mercury (MeHg; 0.02-2 muM) and inorganic mercury (HgCl2; 0.01-1 muM) increased [Ca2+]i in lymphocytes from rat spleen in a concentration-dependent manner. The effect of MeHg was rapid and the increase of Ca2+ level was sustained in time, while HgCl2 caused a s/ow rise in [Ca2+]i. The effects of mercury compounds did not appear to be associated with alterations of membrane integrity, since there was no significant difference in the extent of MnCl2 quench between control and mercury-treated cells. However, HgCl2 (1 muM) and MeHg (2 muM) appeared to cause membrane damage at longer incubation times (15 min). When cells were incubated in Ca2+-free medium (in the presence of 1 mM EDTA) MeHg still increased [Ca2+]i, though to a lesser extent, while HgCl2 had no effect. Heparin, an inhibitor of inositol 1,4,5,-trisphosphate-induced Ca2+ mobilization partially blocked this rise of [Ca2+]i, while carbonyl cyanide m-chlorophenylhydraxone (CCCP), an inhibitor of mitochondrial function, had a lesser effect. When added together heparin and CCCP almost completely block the response to MeHg. These results suggest that MeHg and HgCl2 exert their effects of [Ca2+]i in different ways: MeHg-induced increases in [Ca2+]i are due to influx from outside the cells as well as to mobilization from intracellular stores, possibly the endoplasmic reticulum, and, to a minor extent, the mitochondria; on the other hand, HgCl2 causes only Ca2+ influx from the extracellular medium.