دورية أكاديمية
DBA-induced caspase-3-dependent apoptosis occurs through mitochondrial translocation of cyt-c in the rat hippocampus.
| العنوان: | DBA-induced caspase-3-dependent apoptosis occurs through mitochondrial translocation of cyt-c in the rat hippocampus. |
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| المؤلفون: | Jiang W; Department of Toxicology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province 150081, P. R. China. gsy@ems.hrbmu.edu.cn., Chen Y, Li B, Gao S |
| المصدر: | Molecular bioSystems [Mol Biosyst] 2017 Aug 22; Vol. 13 (9), pp. 1863-1873. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Royal Society of Chemistry Country of Publication: England NLM ID: 101251620 Publication Model: Print Cited Medium: Internet ISSN: 1742-2051 (Electronic) Linking ISSN: 17422051 NLM ISO Abbreviation: Mol Biosyst Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, UK : Royal Society of Chemistry, 2005- |
| مواضيع طبية MeSH: | Acetates/*pharmacology , Apoptosis/*drug effects , Caspase 3/*metabolism , Cytochromes c/*metabolism , Hippocampus/*metabolism , Mitochondria/*drug effects , Mitochondria/*metabolism, Animals ; Caspase 9/metabolism ; Cytosol/metabolism ; DNA Damage ; Female ; Gene Expression Profiling ; Hippocampus/pathology ; Hippocampus/ultrastructure ; Learning/drug effects ; Male ; Memory/drug effects ; Mitochondria/ultrastructure ; Rats ; Reactive Oxygen Species/metabolism ; Superoxide Dismutase/metabolism |
| مستخلص: | Dibromoacetic acid (DBA), a by-product of disinfection, develops in drinking water during chlorination or ozonation processes. Water intake is the main source of DBA exposure in humans, which is potentially neurotoxic. The present study investigated the neurotoxic effects of DBA by assessing the behavioral and biochemical characteristics of Sprague Dawley rats intragastrically treated with DBA at concentrations of 20, 50 and 125 mg kg -1 body weight for 28 consecutive days. The results indicated that animal weight gain and food consumption were not significantly affected by DBA. However, shuttle box tests showed increases in mistake frequency and reaction latency between the control and high-dose group. We found significant changes in hippocampal neurons by histomorphological observation. Additionally, biochemical analysis indicated enhanced production of reactive oxygen species (ROS) resulting in disruption of cellular antioxidant defense systems including decreased mitochondrial superoxide dismutase (SOD) activity and release of cytochrome c (cyt-c) from mitochondria into the cytosol, which can induce neuronal apoptosis. Furthermore, the increase of cyt-c in the cytosol enhanced caspase-3 and caspase-9 activity, which was confirmed by poly ADP-ribose polymerase-1 (PARP-1) cleavage to its signature fragment of 85 kDa and decreased levels of protein kinase C-δ (PKC-δ) in the hippocampus. Meanwhile, DBA treatment caused differential modulation of apoptosis-associated proteins and mRNAs for phosphorylated apoptosis signal regulating kinase 1 (p-ASK-1), phosphorylated c-jun N-terminal kinase (p-JNK), cyt-c, Bax, Bcl-2, caspase-9 and cleaved caspase-3 accompanied by DNA damage. Taken together, these data indicate that DBA may induce neurotoxicity via caspase-3-dependent apoptosis involving mitochondrial translocation of cyt-c in the rat hippocampus. |
| المشرفين على المادة: | 0 (Acetates) 0 (Reactive Oxygen Species) 7FUW62YY5L (dibromoacetic acid) 9007-43-6 (Cytochromes c) EC 1.15.1.1 (Superoxide Dismutase) EC 3.4.22.- (Caspase 3) EC 3.4.22.- (Caspase 9) |
| تواريخ الأحداث: | Date Created: 20170722 Date Completed: 20180430 Latest Revision: 20180430 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1039/c7mb00246g |
| PMID: | 28731097 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1742-2051 |
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| DOI: | 10.1039/c7mb00246g |