Inositol pyrophosphates mediated the apoptosis induced by hypoxic injury in bone marrow-derived mesenchymal stem cells by autophagy
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, respect...
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| Format: | Article |
| Language: | English |
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BMC
2019-06-01
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| Series: | Stem Cell Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13287-019-1256-3 |
| _version_ | 1811328550371852288 |
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| author | Jingyu Deng Chao Yang Yong Wang Ming Yang Haixu Chen Hongjuan Ning Chengzhu Wang Yanjun Liu Zheng Zhang Taohong Hu |
| author_facet | Jingyu Deng Chao Yang Yong Wang Ming Yang Haixu Chen Hongjuan Ning Chengzhu Wang Yanjun Liu Zheng Zhang Taohong Hu |
| author_sort | Jingyu Deng |
| collection | DOAJ |
| description | 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). |
| first_indexed | 2024-04-13T15:28:15Z |
| format | Article |
| id | doaj.art-bb306ee94eaa43e494ed0f89726087a2 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-04-13T15:28:15Z |
| publishDate | 2019-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-bb306ee94eaa43e494ed0f89726087a22022-12-22T02:41:28ZengBMCStem Cell Research & Therapy1757-65122019-06-0110111310.1186/s13287-019-1256-3Inositol pyrophosphates mediated the apoptosis induced by hypoxic injury in bone marrow-derived mesenchymal stem cells by autophagyJingyu Deng0Chao Yang1Yong Wang2Ming Yang3Haixu Chen4Hongjuan Ning5Chengzhu Wang6Yanjun Liu7Zheng Zhang8Taohong Hu9Postgraduate Training Base in Rocket Army Special Medical Center of the PLA, Jinzhou Medical UniversityDepartment of Blood Transfusion, The Rocket Army Special Medical Center of the PLADepartment 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 KongInstitute of Geriatrics & National Clinical Research Center of Geriatrics Disease, Chinese PLA General HospitalJinzhou Medical UniversityDepartment of Cardiology, The Rocket Army Special Medical Center of the PLADepartment of Cardiology, The Rocket Army Special Medical Center of the PLADepartment of Cardiology, The Rocket Army Special Medical Center of the PLADepartment of Cardiology, The Rocket Army Special Medical Center of the PLAAbstract 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).http://link.springer.com/article/10.1186/s13287-019-1256-3HypoxiaBone marrow mesenchymal stem cells (BM-MSCs)Inositol pyrophosphates (IP7)AutophagyApoptosisAkt/mTOR signaling pathway |
| spellingShingle | Jingyu Deng Chao Yang Yong Wang Ming Yang Haixu Chen Hongjuan Ning Chengzhu Wang Yanjun Liu Zheng Zhang Taohong Hu Inositol pyrophosphates mediated the apoptosis induced by hypoxic injury in bone marrow-derived mesenchymal stem cells by autophagy Stem Cell Research & Therapy Hypoxia Bone marrow mesenchymal stem cells (BM-MSCs) Inositol pyrophosphates (IP7) Autophagy Apoptosis Akt/mTOR signaling pathway |
| title | Inositol pyrophosphates mediated the apoptosis induced by hypoxic injury in bone marrow-derived mesenchymal stem cells by autophagy |
| title_full | Inositol pyrophosphates mediated the apoptosis induced by hypoxic injury in bone marrow-derived mesenchymal stem cells by autophagy |
| title_fullStr | Inositol pyrophosphates mediated the apoptosis induced by hypoxic injury in bone marrow-derived mesenchymal stem cells by autophagy |
| title_full_unstemmed | Inositol pyrophosphates mediated the apoptosis induced by hypoxic injury in bone marrow-derived mesenchymal stem cells by autophagy |
| title_short | Inositol pyrophosphates mediated the apoptosis induced by hypoxic injury in bone marrow-derived mesenchymal stem cells by autophagy |
| title_sort | inositol pyrophosphates mediated the apoptosis induced by hypoxic injury in bone marrow derived mesenchymal stem cells by autophagy |
| topic | Hypoxia Bone marrow mesenchymal stem cells (BM-MSCs) Inositol pyrophosphates (IP7) Autophagy Apoptosis Akt/mTOR signaling pathway |
| url | http://link.springer.com/article/10.1186/s13287-019-1256-3 |
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