期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 123, 期 -, 页码 8-19出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2018.05.060
关键词
Sulfiredoxin-1; Human ALDH(br) cardiac stem/progenitor cells; Cell survival; Oxidative stress; ERK/NRF2 signaling pathway
资金
- National Institutes of Health [R01HL114951]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL114951] Funding Source: NIH RePORTER
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 (ALDH(br)-hCPCs) with CoPP. Further studies demonstrated that overexpressing SRXN1 enhanced the survival capacity for ALDH(br)-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 ALDH(br)-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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