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. 2018 Jan 23:12:12.
doi: 10.3389/fnins.2018.00012. eCollection 2018.

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

Gaoyang Wang  1 , Yuan Yuan  2 , Lanyue Gao  2 , Xiaoqiong Tan  1 , Guangqian Yang  1 , Fenghong Zhao  1 , Yaping Jin  1
Affiliations

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

Gaoyang Wang et al. Front Neurosci. .

Abstract

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.

Keywords: 1; 2-dichloroethane poisoning; ATP generation; blood brain barrier; brain edema; tight junction associated proteins.

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Figures

Figure 1
Figure 1
Changes in Na+−K+-ATPase and Ca2+-ATPase activity, ATP and lactic acid content in mouse brain cells induced by subacute poisoning of 1,2-DCE. (a) Comparison of Na+-K+-ATPase activity in mouse brain cells among groups; (b) Comparison of Ca2+-ATPase activity in mouse brain cells among groups; (c) Comparison of ATP content in mouse brain among groups. (d) Comparison of lactic acid level in mouse brain among groups. The number of mice were 10 in control group, 9 in group A, 8 in group B, and 8 in group C. Data were given as mean ± SD, and analyzed by One-way ANOVA. Significant difference was defined as P < 0.05. * vs. control group.
Figure 2
Figure 2
Comparison of intracellular free Ca2+ concentration in mouse brain cells among groups. Five mice in each group were selected for this analysis. [Ca2+]i represented concentrations of intracellular free Ca2+. Data were given as mean ± SD, and analyzed by One-way ANOVA. Significant difference was defined as P < 0.05. *, vs. control group.
Figure 3
Figure 3
Comparison of ZO-1 protein expression in mouse brain among groups (scale bar = 25 μm). Five mice were selected in each group. Data were given as mean ± SD, and analyzed by one-way ANOVA. Significant difference was defined as P < 0.05, * vs. control group. (a) Immunofluorescence staining, green represented ZO-1, and red is for GFAP. A to C represented three exposure groups, in which mice were exposed to 1,2-DCE for 1, 2, or 3days. (b) Comparison of relative fluorescence intensity for ZO-1 among groups.
Figure 4
Figure 4
Comparison of occludin protein expression in mouse brain among groups (scale bar = 25 μm). Five mice were selected in each group. Data were given as mean ± SD, and analyzed by one-way ANOVA. Significant difference was defined as P < 0.05, * vs. control group. (a) Immunofluorescence staining, green represented occludin, and red is for GFAP. A to C represented three exposure groups, in which mice were exposed to 1,2-DCE for 1, 2, or 3 days. (b) Comparison of relative fluorescence intensity for occludin among groups.
Figure 5
Figure 5
Comparison of ZO-1 protein and mRNA levels in mouse brain among groups. The number of mice used for Western blots and real-time RT-PCR were 10 in control, 9 in group A, 8 in group B, and 8 in group C. Data were given as mean ± SD, and analyzed by one-way ANOVA. Significant difference was defined as P < 0.05, * vs. control group. (a) Western blot analysis; (b) Densitometric analysis of Western blots; (c) Quantitation of mRNA by real-time RT-PCR. The mRNA levels were normalized to GAPDH and presented as fold change vs. control group.
Figure 6
Figure 6
Comparison of occludin protein and mRNA levels in mouse brain among groups. The number of mice used for Western blots and real-time RT-PCR were 10 in control, 9 in group A, 8 in group B, and 8 in group C. Data were given as mean ± SD, and analyzed by one-way ANOVA. Significant difference was defined as P < 0.05, * vs. control group. (a) Western blot analysis; (b) Densitometric analysis of Western blots; (c) Quantitation of mRNA by real-time RT-PCR. The mRNA levels were normalized to GAPDH and presented as fold change vs. control group.
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