التفاصيل البيبلوغرافية
| العنوان: |
Diphenylarsinic Acid Induced Activation of Cultured Rat Cerebellar Astrocytes: Phosphorylation of Mitogen-Activated Protein Kinases, Upregulation of Transcription Factors, and Release of Brain-Active Cytokines. |
| المؤلفون: |
Takayuki Negishi, Mami Matsumoto, Mikiya Kojima, Ryota Asai, Tomoko Kanehira, Fumika Sakaguchi, Kazuaki Takahata, Rina Arakaki, Yohei Aoyama, Hikari Yoshida, Kenji Yoshida, Kazunori Yukawa, Tomoko Tashiro, Seishiro Hirano |
| المصدر: |
Toxicological Sciences; Mar2016, Vol. 150 Issue 1, p74-83, 10p, 2 Diagrams, 4 Graphs |
| مصطلحات موضوعية: |
DIPHENYLARSINIC acid, ACTIVATION (Chemistry), LABORATORY rats, CEREBELLAR ataxia, ASTROCYTES, TRANSCRIPTION factors, CYTOKINES |
| مستخلص: |
Diphenylarsinic acid (DPAA) was detected as the primary compound responsible for the arsenic poisoning that occurred in Kamisu, Ibaraki, Japan, where people using water from a well that was contaminated with a high level of arsenic developed neurological (mostly cerebellar) symptoms and dysregulation of regional cerebral blood flow. To understand the underlying molecular mechanism of DPAA-induced cerebellar symptoms, we focused on astrocytes, which have a brain-protective function. Incubation with 10 mM DPAA for 96h promoted cell proliferation, increased the expression of antioxidative stress proteins (heme oxygenase-1 and heat shock protein 70), and induced the release of cytokines (MCP-1, adrenomedullin, FGF2, CXCL1, and IL-6). Furthermore, DPAA overpoweringly increased the phosphorylation of three major mitogenactivated protein kinases (MAPKs) (ERK1/2, p38MAPK, and SAPK/JNK), which indicated MAPK activation, and subsequently induced expression and/or phosphorylation of transcription factors (Nrf2, CREB, c-Jun, and c-Fos) in cultured rat cerebellar astrocytes. Structure-activity relationship analyses of DPAA and other related pentavalent organic arsenicals revealed that DPAA at 10 mM activated astrocytes most effective among organic arsenicals tested at the same dose. These results suggest that in a cerebellum exposed to DPAA, abnormal activation of the MAPK-transcription factor pathway and irregular secretion of these neuroactive, glioactive, and/or vasoactive cytokines in astrocytes can be the direct/indirect cause of functional abnormalities in surrounding neurons, glial cells, and vascular cells: This in turn might lead to the onset of cerebellar symptoms and disruption of cerebral blood flow. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |