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

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.

Involvement of CYP2E1 in the Course of Brain Edema Induced by Subacute Poisoning With 1,2-Dichloroethane in Mice

“…Moreover, combined with the changes of tight junction proteins in the intervention groups, it has been proposed that ROS and reactive metabolites generated in the CYP2E1-mediated metabolism of 1,2-DCE might be involved in the disruption of tight junction proteins. In our previous study, it was reported that the expression levels of both ZO-1 and occludin decreased markedly at the early phase of brain edema, induced by subacute poisoning with 1,2-DCE ( Wang et al, 2018 ), consistent with present findings. In the current study, for the first time, we report the changes of claudin-5 expression in the brains of 1,2-DCE-poisoned mice and the association between the metabolism of 1,2-DCE and the disruption of tight junction proteins in the BBB.…”

Introducing an expanded CAG tract into the huntingtin gene causes a wide spectrum of ultrastructural defects in cultured human cells

“…This analysis revealed structural defects of mitochondria (cristae, matrix, and envelope) together with proliferation of their contacts with the ER. We can hypothesize that these alterations should significantly disturb the energy-dependent metabolism of cells and the balance of Ca 2+ between mitochondria and the cytoplasm as demonstrated in other studies on HD [ 28 , 57 ]. The uncovered accumulation of early and late autolysosomes in mutant cells together with artificial vacuolization of large organelles and disruption of integrity of their limiting membrane in 6H mutant cells strongly correlate with the point of involvement of the HTT protein in stimulation of autophagy in the early period and dysregulation of this process at later stages.…”

Polygenic risk for circulating reproductive hormone levels and their influence on hippocampal volume and depression susceptibility

“…The hippocampus is a major target of estrogens in the brain due its high density of estrogen receptors which have the capacity to influence hippocampal volume through multiple actions, including altered gene expression, differential methylation of estrogen-responsive genes or by rapid-non genomic signaling pathways (Duarte-Guterman et al, 2015; Guintivano et al, 2014; Sárvári et al, 2015; Soma et al, 2018). Our results reveal an enrichment of estradiol’s effect on ‘neurogenic regions’ of the hippocampus, namely the granule cell layer and molecular layer of the dentate gyrus.…”