Cannabinoid-Induced Autophagy and Heme Oxygenase-1 Determine the Fate of Adipose Tissue-Derived Mesenchymal Stem Cells under Stressful Conditions
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Cell Culture
2.3. Cell Metabolic Activity Assay
2.4. Trypan Blue Staining
2.5. siRNA Transfection
2.6. Quantitative RT-PCR Analysis
2.7. Western Blot Analysis
2.8. Statistics
3. Results
3.1. CBD Induces HO-1 mRNA and Protein Expression in ADMSCs under Serum-Free Conditions
3.2. CBD and MA Increase Metabolic Activity and Autophagy of ADMSCs under Serum-Free Conditions
3.3. Cannabinoid-Binding Receptors Mediate neither the CBD-Increased HO-1 Expression nor the CBD- and MA-Increased Metabolic Activity of ADMSCs
3.4. HO-1 Does not Mediate the CBD-Induced Increase in Metabolic Activity and Autophagy of ADMSCs
3.5. Inhibition of Autophagy Leads to a Decrease in the Metabolic Activity Elevated by CBD and MA, to an Increase in Caspase-3 Cleavage, and to the Induction of HO-1 Expression in MA-Treated ADMSCs
3.6. Inhibition of HO-1 Significantly Suppresses Apoptosis of ADMSCs Treated with Cannabinoids and the Autophagy Inhibitor Bafilomycin A1
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Treatment Groups | CB Corresponds to CBD (3 µM) | CB Corresponds to MA (3 µM) | ||
---|---|---|---|---|
Metabolic Activity (%) | HO-1 Protein (%) | HO-2 Protein (%) | Metabolic Activity (%) | |
Vehicle | 100 ± 35 | 100 ± 9 | 100 ± 4 | 100 ± 8 |
CB | 202 ± 50 | 515 ± 30 * | 109 ± 8 | 205 ± 23 * |
CB + AM-630 | 205 ± 40 | 624 ± 108 | 102 ± 3 | 214 ± 26 |
CB + AM-251 | 242 ± 83 | 488 ± 75 | 89 ± 9 | 237 ± 29 |
CB + AM-630 + AM-251 | 220 ± 83 | 499 ± 91 | 89 ± 10 | 217 ± 23 |
CB + Capsa | 211 ± 59 | 615 ± 122 | 89 ± 8 | 242 ± 18 |
Vehicle | 100 ± 35 | 100 ± 18 | 100 ± 6 | 100 ± 26 |
AM-630 | 88 ± 6 | 127 ± 19 | 125 ± 9 | 87 ± 4 |
AM-251 | 125 ± 15 | 216 ± 75 | 123 ± 6 | 110 ± 9 |
AM-630 + AM-251 | 144 ± 19 | 218 ± 88 | 126 ± 19 | 120 ± 3 |
Capsa | 93 ± 3 | 124 ± 13 | 122 ± 18 | 108 ± 5 |
Treatment Groups | Metabolic Activity (%) | HO-1 Protein (%) |
---|---|---|
Vehicle | 100 ± 29 | 100 ± 16 |
3 µM CBD | 174 ± 32 | 277 ± 64 |
CBD + O-1602 | 188 ± 33 | 255 ± 61 |
O-1602 | 106 ± 10 | 103 ± 21 |
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Bublitz, K.; Böckmann, S.; Peters, K.; Hinz, B. Cannabinoid-Induced Autophagy and Heme Oxygenase-1 Determine the Fate of Adipose Tissue-Derived Mesenchymal Stem Cells under Stressful Conditions. Cells 2020, 9, 2298. https://doi.org/10.3390/cells9102298
Bublitz K, Böckmann S, Peters K, Hinz B. Cannabinoid-Induced Autophagy and Heme Oxygenase-1 Determine the Fate of Adipose Tissue-Derived Mesenchymal Stem Cells under Stressful Conditions. Cells. 2020; 9(10):2298. https://doi.org/10.3390/cells9102298
Chicago/Turabian StyleBublitz, Katharina, Sabine Böckmann, Kirsten Peters, and Burkhard Hinz. 2020. "Cannabinoid-Induced Autophagy and Heme Oxygenase-1 Determine the Fate of Adipose Tissue-Derived Mesenchymal Stem Cells under Stressful Conditions" Cells 9, no. 10: 2298. https://doi.org/10.3390/cells9102298