دورية أكاديمية
Role of Mitofusin-2 in High Mobility Group Box-1 Protein-Mediated Apoptosis of T Cells in Vitro
| العنوان: | Role of Mitofusin-2 in High Mobility Group Box-1 Protein-Mediated Apoptosis of T Cells in Vitro |
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| المؤلفون: | Zong-sheng Wu, Yong-ming Yao, Guang-liang Hong, Xiu-ping Xu, Yao Liu, Ning Dong, Jia-yi Zheng, Zhong-qiu Lu, Guang-ju Zhao, Xiao-mei Zhu, Qing-hong Zhang, Zhi-yong Sheng |
| المصدر: | Cellular Physiology and Biochemistry, Vol 33, Iss 3, Pp 769-783 (2014) |
| بيانات النشر: | Cell Physiol Biochem Press GmbH & Co KG, 2014. |
| سنة النشر: | 2014 |
| المجموعة: | LCC:Physiology LCC:Biochemistry |
| مصطلحات موضوعية: | High mobility group box-1 protein (HMGB1), Jurkat T cells, Apoptosis, Mitofusin-2(Mfn2), Calcium, Physiology, QP1-981, Biochemistry, QD415-436 |
| الوصف: | Background: High mobility group box-1 protein (HMGB1), a ubiquitous nuclear protein, which is recognized as a danger-associated molecular pattern (DAMP) triggering activation of the innate immune system. Previous studies have shown that HMGB1 also plays a role in T cell-mediated immunity, but the effect of HMGB1 on apoptosis of T cells and its precise mechanism remain to be determined. Methods: Two kinds of apoptosis assay techniques were used, i.e., Annexin V-FITC conjunction with PI to identify early apoptotic cells, Hoechst 33342 staining for double-stranded DNA to observe nuclear fragmentation or apoptotic body. The activation status of caspase-3, caspase-8, as well as caspase-9 was examined by colorimetric assay. The dynamic changes in intracellular calcium concentration ([Ca2+]i) was monitored by flow cytometry. Overexpression of Mfn2 was preformed by lentiviral vector transfection. The mRNA and protein levels of Mfn2 were determined by RT-PCR and Western-blotting. Results: Treatment of Jurkat T cells with recombinant human HMGB1 (rhHMGB1) causes a significant dose-dependent increase in percentage of apoptotic cells. When T cells are incubated with HMGB1 they express decreased mitochondria fusion-related protein mitofusin-2 (Mfn2) and activate mitochondrial apoptotic pathway via elevation of [Ca2+]i, Bax insertion, and activation of caspase. Furthermore, overexpression of Mfn2 ameliorates the apoptosis of T cells induced by HMGB1. This occurs at least partly through Mfn2 keeps Ca2+ homeostasis in T cells evidenced by monitoring [Ca2+]i dynamics. Conclusion: HMGB1 can trigger apoptosis of T lymphocytes through mitochondrial death pathway associated with [Ca2+]i elevation. Mfn2 plays a pivotal role in this process, and it might be a novel therapeutic target in T cell apoptosis related disorders. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1015-8987 1421-9778 |
| Relation: | http://www.karger.com/Article/FullText/358651; https://doaj.org/toc/1015-8987; https://doaj.org/toc/1421-9778 |
| DOI: | 10.1159/000358651 |
| URL الوصول: | https://doaj.org/article/d3aa5422cbd04dbc9c354d45978e9c58 |
| رقم الأكسشن: | edsdoj.3aa5422cbd04dbc9c354d45978e9c58 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 10158987 14219778 |
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| DOI: | 10.1159/000358651 |