CoQ10 Deficient Endothelial Cell Culture Model for the Investigation of CoQ10 Blood–Brain Barrier Transport
Abstract
:1. Introduction
2. Experimental Section
2.1. Materials
2.2. CoQ10 Analysis by Liquid Chromatography-Tandem Mass Spectrometry
2.3. Blood–Brain Barrier Cell Culture
2.4. Coenzyme Q10 Transport Assays
2.5. Cellular CoQ10 Depletion and Mitochondrial Respiratory Chain Enzyme Activity
2.6. Cell Viability Assay
2.7. CoQ10 Partition in Serum Lipoprotein Fractions
2.8. Confocal Microscopy
2.9. Statistical Analysis
3. Results
3.1. LC-MS/MS CoQ10 Method Validation
3.2. Effect of Serum Pre-Incubation on CoQ10 Transport across In Vitro BBB
3.3. CoQ10 Distribution in Serum Lipoprotein Fractions
3.4. CoQ10 BBB Transport: SR-B1, LDLR, and RAGE Inhibitors
3.5. Inhibition of CoQ10 Biosynthesis
3.6. CoQ10 Defecient BBB: Effect of SR-B1, LDLR, and RAGE Inhibitors
3.7. Effect of Antioxidants on CoQ10 BBB Transport
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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LC-MS/MS | HPLC-UV | |
---|---|---|
LLOQ (nmol/L) | 0.25 | 10 |
LLOD (nmol/L) | 0.125 | 6 |
Linearity (nmol/L) | 500 | 200 |
Run Time (minutes) | 7 | 25 |
Intra-Assay Imprecision (CV%) | Inter-Assay Imprecision (CV%) | Recovery (Ave.%) | |
---|---|---|---|
Baseline | 3.6 | 7.2 | − |
Low Spike (10 nmol/L) | 5.6 | 6.4 | 84 |
High Spike (100 nmol/L) | 5.9 | − | 103 |
EQC Plasma | − | 6.7 | − |
Lipoprotein Fraction | Untreated Serum CoQ10 nmol/L | Supplemented Serum CoQ10 nmol/L |
---|---|---|
HDL | 32.7 ± 1.8 (21.7%) | 762 ± 8.1 (7.2%) |
LDL | 117.0 ± 1.2 (77.7%) | 6718 ± 103.5 (63.8%) |
vLDL | 0.9 ± 0.01 (0.6%) | 3060 ± 138.8 (29.0%) |
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Wainwright, L.; Hargreaves, I.P.; Georgian, A.R.; Turner, C.; Dalton, R.N.; Abbott, N.J.; Heales, S.J.R.; Preston, J.E. CoQ10 Deficient Endothelial Cell Culture Model for the Investigation of CoQ10 Blood–Brain Barrier Transport. J. Clin. Med. 2020, 9, 3236. https://doi.org/10.3390/jcm9103236
Wainwright L, Hargreaves IP, Georgian AR, Turner C, Dalton RN, Abbott NJ, Heales SJR, Preston JE. CoQ10 Deficient Endothelial Cell Culture Model for the Investigation of CoQ10 Blood–Brain Barrier Transport. Journal of Clinical Medicine. 2020; 9(10):3236. https://doi.org/10.3390/jcm9103236
Chicago/Turabian StyleWainwright, Luke, Iain P. Hargreaves, Ana R. Georgian, Charles Turner, R. Neil Dalton, N. Joan Abbott, Simon J. R. Heales, and Jane E. Preston. 2020. "CoQ10 Deficient Endothelial Cell Culture Model for the Investigation of CoQ10 Blood–Brain Barrier Transport" Journal of Clinical Medicine 9, no. 10: 3236. https://doi.org/10.3390/jcm9103236