Cyclosporin A pre-incubation attenuates hypoxia/reoxygenation-induced apoptosis in mesenchymal stem cells
Cyclosporin A pre-incubation attenuates hypoxia/reoxygenation-induced apoptosis in mesenchymal stem cells
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DOI：
10.1080/00365510801918761
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发表时间：
2008-01-01
影响因子：
2.1
通讯作者：
Cao, J.
中科院分区：
文献类型：
--
作者：
Chen, T. -L.;Wang, J. -A.;Cao, J.
虽然间充质干细胞（MSCs）被用于心脏修复试验，但由于缺血/再灌注、血供不良和其他促凋亡因子的影响，大多数移植细胞在缺血心脏中发生凋亡。一些实验和临床研究表明，环孢素A （CsA）治疗可减少人内皮细胞和神经细胞的凋亡。然而，CsA对MSCs细胞凋亡的影响尚不清楚。在本研究中，我们研究了CsA是否可以抑制缺氧/再氧化（H/R）诱导的MSCs凋亡。加CsA或不加CsA预孵育的MSCs进行6小时缺氧，然后再加氧12小时。我们的数据显示，预孵育0.5-5 μ M CsA剂量依赖性地保护MSCs免受H/R损伤，证明了细胞凋亡减少和细胞活力增加。CsA抑制H/ r诱导的细胞色素c易位，增加bcl-2表达，恢复线粒体膜电位。CsA也增加了p-BAD的表达。我们提出CsA在培养前通过线粒体和BAD途径抑制MSC凋亡。
Although mesenchymal stem cells (MSCs) are being tested for cardiac repair, the majority of transplanted cells undergo apoptosis in the ischaemic heart because of the effects of ischaemia/reperfusion, poor blood supply and other pro-apoptotic factors. Several experimental and clinical studies have suggested that cyclosporin A (CsA) treatment reduces apoptosis in human endothelial cells and neurocytes. However, the effect of CsA on the apoptosis in MSCs is still unclear. In this study, we investigated whether CsA could inhibit hypoxia/reoxygenation (H/R)-induced apoptosis in MSCs. MSCs pre-incubated with or without CsA were subjected to 6 h of hypoxia followed by 12 h of reoxygenation. Our data showed that pre-incubation with 0.5-5 mu M CsA dose-dependently protected the MSCs from H/R injury, as evidenced by decreased apoptosis and increased cell viability. CsA inhibited the H/R-induced translocation of cytochrome c, increased bcl-2 expression and restored mitochondrial membrane potential. CsA also increased the expression of p-BAD. We propose that pre-incubation MSCs with CsA inhibits MSC apoptosis through the mitochondrial and BAD pathway.