Fr-HMGB1 and ds-HMGB1 activate the kynurenine pathway via different mechanisms in association with depressive-like behavior
| العنوان: | Fr-HMGB1 and ds-HMGB1 activate the kynurenine pathway via different mechanisms in association with depressive-like behavior |
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| المؤلفون: | Jia‑Mei Li, Wen‑Jun Su, Yong‑Jie Lian, Bo Wang, Lin‑Lin Liu, Chun‑Lei Jiang, Yun‑Xia Wang |
| المصدر: | Molecular Medicine Reports |
| بيانات النشر: | D.A. Spandidos, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Kynurenine pathway, fully reduced high mobility group box 1, medicine.medical_treatment, neuroinflammatory cytokines, Interleukin-1beta, chemical and pharmacologic phenomena, Enzyme-Linked Immunosorbent Assay, Pharmacology, HMGB1, Biochemistry, Hippocampus, 03 medical and health sciences, Mice, 0302 clinical medicine, Downregulation and upregulation, Western blot, Genetics, medicine, Animals, Humans, Disulfides, RNA, Messenger, HMGB1 Protein, Molecular Biology, Kynurenine, Depressive Disorder, Oncogene, biology, medicine.diagnostic_test, Behavior, Animal, Chemistry, Depression, Tumor Necrosis Factor-alpha, Articles, Hydrogen Peroxide, 030104 developmental biology, Cytokine, Oncology, Apoptosis, 030220 oncology & carcinogenesis, disulfide high mobility group box 1, biology.protein, Molecular Medicine, Tumor necrosis factor alpha, kynurenine pathway |
| الوصف: | Our previous study reported that fully reduced high mobility group box 1 (fr‑HMGB1) and disulfide HMGB1 (ds‑HMGB1) induce depressive‑like behavior; however, the underlying mechanisms remain unclear. In the present study, the induction of depression via the kynurenine pathway by different redox states of HMGB1 was investigated in vivo and in vitro. To evaluate the expression of enzymes of the kynurenine pathway, reverse transcription‑quantitative PCR and western blot analyses were conducted. Additionally, cytokine levels were measured by ELISAs. Following intracerebroventricular injection of ds‑ and fr‑HMGB1, behavioral tests were performed, revealing the presentation of depressive‑like behavior, and essential proteins in the kynurenine pathway were demonstrated to be upregulated at the mRNA level, suggesting that ds‑ and fr‑HMGB1 contributed to the development of this behavior via the kynurenine pathway. ds‑HMGB1 directly activated the kynurenine pathway and cytokines such as tumor necrosis factor‑α (TNF‑α) and interleukin‑1β (IL‑1β) in the hippocampal tissue. Conversely, fr‑HMGB1 upregulated the aforementioned factors only following treatment with H2O2. These findings indicated that ds‑HMGB1 induced depression in a manner associated with the kynurenine pathway, whereas oxidation of fr‑HMGB1 evoked activation of the kynurenine pathway, resulting in depressive behavior. |
| اللغة: | English |
| تدمد: | 1791-3004 1791-2997 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cfceae78e17507b1a0ab9704dc784a12Test http://europepmc.org/articles/PMC6580048Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....cfceae78e17507b1a0ab9704dc784a12 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17913004 17912997 |
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