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, 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).

• Authors: Jingyu Deng, Chao Yang, Yong Wang, Ming Yang, Haixu Chen, Hongjuan Ning, Chengzhu Wang, Yanjun Liu, Zheng Zhang, Taohong Hu
• Journal: Stem cell research & therapy (Stem Cell Res Ther) Vol. 10 Issue 1 Pg. 159 (06 03 2019) ISSN: 1757-6512 [Electronic] England
• PMID: 31159888 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• mTOR protein, mouse
• Proto-Oncogene Proteins c-akt
• TOR Serine-Threonine Kinases

Topics

• Animals
• Apoptosis (genetics, physiology)
• Autophagy (physiology)
• Blotting, Western
• Bone Marrow Cells (cytology)
• Cell Hypoxia (genetics, physiology)
• Flow Cytometry
• In Situ Nick-End Labeling
• Male
• Mesenchymal Stem Cells (cytology, metabolism)
• Mice
• Mice, Inbred C57BL
• Plasmids (genetics)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Signal Transduction
• TOR Serine-Threonine Kinases (genetics, metabolism)