Sulfiredoxin-1 enhances cardiac progenitor cell survival against oxidative stress via the upregulation of the ERK/NRF2 signal pathway.
Sulfiredoxin-1 enhances cardiac progenitor cell survival against oxidative stress via the upregulation of the ERK/NRF2 signal pathway.
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DOI：
10.1016/j.freeradbiomed.2018.05.060
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发表时间：
2018-08-01
影响因子：
7.4
通讯作者：
Cai C
中科院分区：
文献类型：
--
作者：
Li X;He P;Wang XL;Zhang S;Devejian N;Bennett E;Cai C
心脏干/祖细胞（CPCs）最近已成为一种潜在的变革性再生医学，以修复梗死的心脏。然而，供体细胞的有限存活是CPC治疗的主要挑战之一。我们最近对钴原卟啉（CoPP）预处理人CPC（hCPC）的研究结果表明，硫氧还蛋白-1（SRXN1）在CoPP预处理醛脱氢酶亮hCPC（ALDHbr-hCPC）后上调。进一步的研究表明，过表达SRXN1增强了ALDHbr-hCPC的存活能力。这与包括BCL 2和BCL-xL在内的抗凋亡因子的上调有关。同时，SRXN1过表达降低了ROS的产生和线粒体膜电位，并上调了PRDX1、PRDX3、TXNRD1、过氧化氢酶和SOD 2等主要抗氧化系统。还观察到过表达SRXN1增加ALDHbr-hCPC的迁移、增殖和心脏分化。有趣的是，SRXN1激活ERK/NRF2细胞存活信号通路，这可能是过表达SRXN1导致保护hCPC免受氧化应激诱导的凋亡的潜在机制。总之，这些结果为探索SRXN1作为一种新的分子靶点提供了理论基础，该靶点可用于增强心脏干/祖细胞治疗缺血性心脏病的有效性。
Cardiac stem/progenitor cells (CPCs) have recently emerged as a potentially transformative regenerative medicine to repair the infarcted heart. However, the limited survival of donor cells is one of the major challenges for CPC therapy. Our recent research effort on preconditioning human CPCs (hCPCs) with cobalt protoporphyrin (CoPP) indicated that sulfiredoxin-1 (SRXN1) is upregulated upon preconditioning aldehyde dehydrogenase bright hCPCs (ALDHbr-hCPCs) with CoPP. Further studies demonstrated that overexpressing SRXN1 enhanced the survival capacity for ALDHbr-hCPCs. This was associated with the up-regulation of anti-apoptotic factors, including BCL2 and BCL-xL. Meanwhile, overexpressing SRXN1 decreased the ROS generation and mitochondrial membrane potential, concomitant with the up-regulated primary antioxidant systems, such as PRDX1, PRDX3, TXNRD1, Catalase and SOD2. It was also observed that overexpressing SRXN1 increased the migration, proliferation, and cardiac differentiation of ALDHbr-hCPCs. Interestingly, SRXN1 activated the ERK/NRF2 cell survival signaling pathway, which may be the underlying mechanism through which overexpressing SRXN1 lead to protection of hCPCs against oxidative stress-induced apoptosis. Taken together, these results provide a rationale for the exploration of SRXN1 as a novel molecular target that can be used to enhance the effectiveness of cardiac stem/progenitor cell therapy for ischemic heart disease.
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影响因子：
9.5
作者：
Hong KU;Li QH;Guo Y;Patton NS;Moktar A;Bhatnagar A;Bolli R
通讯作者：
Bolli R
DOI：
10.1038/nrm3772
发表时间：
2014-04
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
8
作者：
Lei, K.;Townsend, D. M.;Tew, K. D.
通讯作者：
Tew, K. D.
影响因子：
4.6
作者：
Bigarella, Carolina L.;Liang, Raymond;Ghaffari, Saghi
通讯作者：
Ghaffari, Saghi
影响因子：
7.4
作者：
Abbas, Kahina;Breton, Jacques;Drapier, Jean-Claude
通讯作者：
Drapier, Jean-Claude