NGF mediates protection of mesenchymal stem cells-conditioned medium against 2,5-hexanedione-induced apoptosis of VSC4.1 cells via Akt/Bad pathway

• Published in: Molecular and cellular biochemistry 2020-06, Vol.469 (1-2), p.53-64
• Main Authors: Bai, Qiufang, Zou, Ming, Zhang, Jizhi, Tian, Ye, Wu, Fei, Gao, Bihu, Piao, Fengyuan
• Format: Article
• Language: English
• Subjects: AKT protein; Animals; Antibodies; Apoptosis; Apoptosis - drug effects; bcl-Associated Death Protein - metabolism; Biochemistry; Biomedical and Life Sciences; Cardiology; Caspase 3 - metabolism; Caspase-3; Culture Media, Conditioned - pharmacology; Cytochrome c; Cytochromes; Cytochromes c - metabolism; Hexanones - toxicity; High-definition television; Life Sciences; Medical Biochemistry; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Microscopy, Electron, Transmission; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Nerve growth factor; Nerve Growth Factor - metabolism; Nerve Growth Factor - pharmacology; Neurons - drug effects; Neurons - metabolism; Neurons - ultrastructure; Oncology; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Rats; Receptor, trkA - antagonists & inhibitors; Signal Transduction - drug effects; Stem cells; TrkA protein
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-020-03727-5

It has been shown that the conditioned medium of bone mesenchymal stem cells (BMSC-CM) can inhibit apoptosis of neural cells exposed to 2,5-hexanedione (HD), but its protective mechanism remains unclear. To investigate the underlying mechanism, VSC4.1 cells were given HD and 5, 10 and 15% BMSC-CM (v/v) in the current experiment. Our data showed that BMSC-CM concentration-dependently attenuated HD-induced cell apoptosis. Moreover, BMSC-CM remarkably decreased the mitochondrial cytochrome c (Cyt C) release and the caspase-3 activity in HD-given VSC4.1 cells. Given a relatively high expression of NGF in BMSCs and BMSC-CM, we hypothesized that NGF might be an important mediator of the protection of BMSC-CM against apoptosis induced by HD. To verify our hypothesis, the VSC4.1 cells were administrated with NGF and anti-NGF antibody in addition to HD. As expected, NGF could perfectly mimic BMSC-CM’s protective role and these beneficial effects were abolished by anti-NGF antibody intervention. To further explore its mechanism, inhibitors of TrkA and Akt were given to the VSC4.1 cells and NGF/Akt/Bad pathway turned out to be involved in anti-apoptotic role of BMSC-CM. Based on these findings, it was revealed that BMSC-CM beneficial role was mediated by NGF and relied on the Akt/Bad pathway.