Inositol pyrophosphates mediated the apoptosis induced by hypoxic injury in bone marrow-derived mesenchymal stem cells by autophagy

Stem Cell Research & Therapy

Chao Yang¹  Taohong Hu²  Zheng Zhang²  Yanjun Liu²  Chengzhu Wang²  Yong Wang³  Ming Yang⁴  Haixu Chen⁵  Hongjuan Ning⁶  Jingyu Deng⁷ 

[1] Department of Blood Transfusion, The Rocket Army Special Medical Center of the PLA;Department of Cardiology, The Rocket Army Special Medical Center of the PLA;Department of Nuclear Medicine, the Fifth Medical Center, Chinese PLA General Hospital (Former 307th hospital of the PLA);Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong;Institute of Geriatrics & National Clinical Research Center of Geriatrics Disease, Chinese PLA General Hospital;Jinzhou Medical University;Postgraduate Training Base in Rocket Army Special Medical Center of the PLA, Jinzhou Medical University;

关键词: Hypoxia;    Bone marrow mesenchymal stem cells (BM-MSCs);    Inositol pyrophosphates (IP7);    Autophagy;    Apoptosis;    Akt/mTOR signaling pathway;   

DOI  :  10.1186/s13287-019-1256-3

来源: DOAJ

【 摘 要 】

Abstract Objective To investigate the potential effect of IP7 on the autophagy and apoptosis of bone marrow mesenchymal stem cells (BM-MSCs) caused by hypoxia. Methods BM-MSCs isolated from adult male C57BL/6 mice were exposed to normoxic condition and hypoxic stress for 6 h, 12 h, and 24 h, respectively. Then, flow cytometry detected the characteristics of BM-MSCs. Furthermore, N6-(p-nitrobenzyl) purine (TNP) was administrated to inhibit inositol pyrophosphates (IP7). TUNEL assay determined the apoptosis in BM-MSCs with hypoxia. Meanwhile, RFP-GFP-LC3 plasmid transfection and transmission microscope was used for measuring autophagy. In addition, Western blotting assay evaluated protein expressions. Results Hypoxic injury increased the autophagy and apoptosis of BM-MSCs. At the same time, hypoxic injury enhanced the production of IP7. Moreover, hypoxia decreased the activation of Akt/mTOR signaling pathway. At last, TNP (inhibitor of IP7) repressed the increased autophagy and apoptosis of BM-MSCs under hypoxia. Conclusion The present study indicated that hypoxia increased autophagy and apoptosis via IP7-mediated Akt/mTOR signaling pathway of BM-MSCs. It may provide a new potential therapy target for myocardial infarction (MI).

【 授权许可】

Unknown