Disruption of Intracellular ATP Generation and Tight Junction Protein Expression during the Course of Brain Edema Induced by Subacute Poisoning of 1,2-Dichloroethane.

Disruption of Intracellular ATP Generation and Tight Junction Protein Expression during the Course of Brain Edema Induced by Subacute Poisoning of 1,2-Dichloroethane.
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1,2-二氯乙烷亚急性中毒脑水肿过程中细胞内ATP生成和紧密连接蛋白表达的破坏

DOI:
10.3389/fnins.2018.00012
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发表时间:
2018
影响因子:
4.3
通讯作者:
Jin Y
Jin Y
中科院分区:
医学2区
文献类型:
--
作者:
Wang G;Yuan Y;Gao L;Tan X;Yang G;Zhao F;Jin Y

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探讨1,2-二氯乙烷(1,2-dichloroethane,1,2-DCE)亚急性中毒致脑水肿过程中细胞内ATP生成和紧密连接蛋白表达的变化。将小鼠暴露于1.2 g/m3的1,2-DCE中,每天3.5 h,持续1、2或3 d,即A、B和C组。测定脑组织Na+-K+-ATP酶、Ca 2 +-ATP酶活性、ATP含量、乳酸含量、细胞内游离Ca 2+浓度、ZO-1和occludin表达。结果显示,与对照组相比,B、C组细胞内Ca ~(2+)-ATP酶活性降低,Na ~+/K ~+-ATP酶活性降低,而B、C组细胞内游离Ca ~(2+)浓度升高。与对照组相比,C组ATP含量显著降低,而乳酸含量显著升高。而ZO-1和occludin在B和C组的蛋白和基因表达水平均较对照组显著降低。总之,本研究的结果表明,钙超载和紧密连接相关蛋白,如ZO-1和occludin的表达抑制可能在亚急性中毒1,2-DCE引起的脑水肿形成的早期阶段发挥重要作用。
The aim of this study was to explore changes in intracellular ATP generation and tight junction protein expression during the course of brain edema induced by subacute poisoning of 1,2-dichloroethane (1,2-DCE). Mice were exposed to 1.2 g/m3 1,2-DCE for 3.5 h per day for 1, 2, or 3 days, namely group A, B, and C. Na+-K+-ATPase and Ca2+-ATPase activity, ATP and lactic acid content, intracellular free Ca2+ concentration and ZO-1 and occludin expression in the brain were measured. Results of present study disclosed that Ca2+-ATPase activities in group B and C, and Na+/K+-ATPase activity in group C decreased, whereas intracellular free Ca2+ concentrations in group B and C increased significantly compared with control. Moreover, ATP content decreased, whereas lactic acid content increased significantly in group C compared with control. On the other hand, expressions of ZO-1 and occludin at both the protein and gene levels in group B and C decreased significantly compared with control. In conclusion, findings from this study suggest that calcium overload and depressed expression of tight junction associated proteins, such as ZO-1 and occludin might play an important role in the early phase of brain edema formation induced by subacute poisoning of 1,2-DCE.
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DOI: 10.1016/j.neuroscience.2012.08.043
发表时间: 2012-12-13
期刊: NEUROSCIENCE
影响因子: 3.3
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