| 支链氨基酸氨基转移酶1通过P53信号调节脂肪间充质干细胞存活 |
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| 引用本文： | 宋丹丹,胡洸瑜,张富洋,高峰,孙芳芳,崔哲,陶凌,宋延彬.支链氨基酸氨基转移酶1通过P53信号调节脂肪间充质干细胞存活[J].心脏杂志,2022,34(3):256-261. |
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| 作者姓名： | 宋丹丹 胡洸瑜 张富洋 高峰 孙芳芳 崔哲 陶凌 宋延彬 |
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| 作者单位： | 1.延安大学附属医院心内科, 陕西 延安 716000 |
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| 基金项目： | 国家自然科学基金项目资助（81730011，81800326，82170337，81760069） |
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| 摘 要： | 目的 研究支链氨基酸氨基转移酶1(branched-chain-amino-acid aminotransferase 1，BCAT1)调节间充质干细胞存活的作用并探讨机制。 方法 从雄性Sprague Dawley大鼠附睾白色脂肪中分离脂肪间充质干细胞（adipose-derived mesenchymal stem cells，ADSCs）。腺病毒转染ADSCs中分别过表达或敲低BCAT1表达后给予过氧化氢（hydrogen dioxide，H2O2）刺激诱导ADSCs凋亡。利用CCK-8细胞活力分析、cleaved caspase-3表达及TUNEL染色评估ADSCs凋亡。利用P53特异性抑制剂PFT-1α探讨P53信号在BCAT1调节ADSCs生存的分子机制。 结果 BCAT1而不是BCAT2是ADSCs的主要表达亚型。H2O2刺激诱导ADSCs凋亡时BCAT1蛋白表达水平显著降低（P<0.01）。使用shRNA敲低BCAT1表达加重而过表达BCAT1显著减轻H2O2诱导的ADSCs凋亡（均P<0.01）。敲低BCAT1导致H2O2刺激的ADSCs中P53下游靶基因表达水平显著增高，提示P53信号活化（均P<0.01）。PFT-1α可以逆转BCAT1敲低恶化的ADSCs凋亡（均P<0.01）。 结论 BCAT1通过P53信号调节ADSCs生存。BCAT1可作为促进ADSCs存活、增强其心肌保护作用的候选靶点。
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| 关 键 词： | BCAT1 P53 间充质干细胞 细胞凋亡 |
| 收稿时间： | 2021-11-29 |
Branched chain amino acid aminotransferase-1 regulates adipose-derived mesenchymal stem cell survival via P53 signaling. |
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| Affiliation: | 1.Department of Cardiology, Affiliated Hospital, Yan’an University, Yan’an 716000, Shaanxi, China2.Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi’an 710032, Shaanxi, China |
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| Abstract: | AIM To determine the regulatory role of branched chain amino acid aminotransferase-1 (BCAT1) in the survival of adipose-derived mesenchymal stem cells (ADSCs). METHODS ADSCs were isolated from white adipose tissues of male Sprague Dawley rats. BCAT1 expression was knocked down or over-expressed in ADSCs by adenovirus transfection and ADSC apoptosis was induced by hydrogen dioxide stimulation. ADSC apoptosis was evaluated by CCK-8 cell viability assay, cleaved caspase-3 expression, and TUNEL staining. The activity of P53 was suppressed by the specific inhibitor PFT-1α in control or BCAT1 silencing ADSCs. RESULTS BCAT1, rather than BCAT2, was the predominant subtype expressed in ADSCs. Silencing of BCAT1 exacerbated, whereas BCAT1 over-expression ameliorated hydrogen dioxide-induced ADSC apoptosis. The downstream targets of P53 were significantly increased in BCAT1 knock-downed ADSCs when stimulated by hydrogen dioxide. Inhibition of P53 by its specific inhibitor PFT-1α reversed the adverse impact of BCAT1 silencing on ADSC survival. CONCLUSION BCAT1 regulates ADSC survival via a P53-dependent manner, revealing that BCAT1 is a promising target to enhance ADSC survival and their cardioprotective efficacy. |
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