Impact of Vitamin D3 Deficiency on Phosphatidylcholine-/Ethanolamine, Plasmalogen-, Lyso-Phosphatidylcholine-/Ethanolamine, Carnitine- and Triacyl Glyceride-Homeostasis in Neuroblastoma Cells and Murine Brain
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals, Reagents and Standards
2.2. Cell Culture and Calcitriol-Treatment
2.3. Animal Experiments
2.4. Sample Preparation
2.5. Targeted Shotgun Mass Spectrometry
2.6. Gene Expression Analysis
2.7. Analysis of Oxygen Consumption
2.8. Data and Statistical Analysis
3. Results
3.1. Phosphatidylcholine (PCaa) Species
3.2. Phosphatidylcholine Plasmalogens (PCae) Species
3.3. Lyso-Phosphatidylcholine (Lyso-PC) Species
3.4. Phosphatidylethanolamine (PE) Species
3.5. Lipid Species Involved in Cellular Energy Metabolism and β-Oxidation
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Lipid Species | Vitamin D Deficiency | Selection of Proposed AD-Related Mechanisms |
---|---|---|
PUFA | ↓ | PUFAs are reported to be decreased in AD due to increased ROS levels. Moreover, in particular DHA is known to affect Aβ production via multiple pleiotropic mechanisms, including an increase of nonamyloidogenic processing by increase of ADAM17 protein levels accompanied by an increase in ADAM17 expression, and a decrease in ADAM17 protein degradation. Furthermore, amyloidogenic APP processing is decreased in presence of PUFAs, resulting in reduced Aβ production. Underlying mechanisms include a decreased BACE1 activity; a changed distribution of BACE1 on the cell surface/intracellular BACE1 pool is discussed. With respect to γ-secretase, a direct effect of DHA on enzyme activity is reported, accompanied by a shift from γ-secretase from raft to nonraft [80]. Further potential mechanisms include effects on Aβ degradation. In particular, EPA has been shown to increase IDE mediated Aβ degradation [81]. Importantly, oxidized PUFA species seem to have controversial effects [82]. |
SFA | ↑ | Saturated fatty acids are reported to be linked with dementia in several studies, reviewed, e.g., in [83]. Potential molecular mechanisms might include an effect of SFA on α-secretase and membrane fluidity (SFAs show a decrease on α-secretase activity and membrane fluidity compared to MUFAs and PUFAs) [64]. In return, SFAs seem to increase β-amyloid secretion and are associated with reduced β-amyloid elimination. Moreover, SFAs are discussed to be associated with an increase in diabetes and insulin resistance, which play a crucial role in AD [84]. |
Lyso-PC | ↑ | Lyso-PCs are reported to be increased during aging and in particular in AD [43,85]. Importantly, a tight link between phospholipase A2, resulting in lyso-PC generation, and Aβ has been reported [86]. In line, PLA2 reduction was shown to ameliorate cognitive deficits in AD mouse models [87]. Additionally, lyso-PC increases neurotoxicity of Aβ1-42, and a potential impact of Aβ oligomerization induced by lyso PCs is discussed [74]. |
Plasmalogens | ↑ | Plasmalogens are known to be decreased in AD brains [88]. Plasmalogens are known to be vulnerable to ROS species, being increased in AD [89]. In return, plasmalogens decrease Aβ generation [90]. Importantly, vitamin D3 deficiency results in an increase in plasmalogens both in murine brain and in cell culture. Further experiments are needed to proof whether vitamin D3 supplementation in human results in decreased plasmalogens levels, which would be unfavorable with respect to AD. Therefore, an additional plasmalogens—in addition to vitamin D3 supplementation—might be useful and should be further investigated with respect to AD. |
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Lauer, A.A.; Griebsch, L.V.; Pilz, S.M.; Janitschke, D.; Theiss, E.L.; Reichrath, J.; Herr, C.; Beisswenger, C.; Bals, R.; Valencak, T.G.; et al. Impact of Vitamin D3 Deficiency on Phosphatidylcholine-/Ethanolamine, Plasmalogen-, Lyso-Phosphatidylcholine-/Ethanolamine, Carnitine- and Triacyl Glyceride-Homeostasis in Neuroblastoma Cells and Murine Brain. Biomolecules 2021, 11, 1699. https://doi.org/10.3390/biom11111699
Lauer AA, Griebsch LV, Pilz SM, Janitschke D, Theiss EL, Reichrath J, Herr C, Beisswenger C, Bals R, Valencak TG, et al. Impact of Vitamin D3 Deficiency on Phosphatidylcholine-/Ethanolamine, Plasmalogen-, Lyso-Phosphatidylcholine-/Ethanolamine, Carnitine- and Triacyl Glyceride-Homeostasis in Neuroblastoma Cells and Murine Brain. Biomolecules. 2021; 11(11):1699. https://doi.org/10.3390/biom11111699
Chicago/Turabian StyleLauer, Anna Andrea, Lea Victoria Griebsch, Sabrina Melanie Pilz, Daniel Janitschke, Elena Leoni Theiss, Jörg Reichrath, Christian Herr, Christoph Beisswenger, Robert Bals, Teresa Giovanna Valencak, and et al. 2021. "Impact of Vitamin D3 Deficiency on Phosphatidylcholine-/Ethanolamine, Plasmalogen-, Lyso-Phosphatidylcholine-/Ethanolamine, Carnitine- and Triacyl Glyceride-Homeostasis in Neuroblastoma Cells and Murine Brain" Biomolecules 11, no. 11: 1699. https://doi.org/10.3390/biom11111699
APA StyleLauer, A. A., Griebsch, L. V., Pilz, S. M., Janitschke, D., Theiss, E. L., Reichrath, J., Herr, C., Beisswenger, C., Bals, R., Valencak, T. G., Portius, D., Grimm, H. S., Hartmann, T., & Grimm, M. O. W. (2021). Impact of Vitamin D3 Deficiency on Phosphatidylcholine-/Ethanolamine, Plasmalogen-, Lyso-Phosphatidylcholine-/Ethanolamine, Carnitine- and Triacyl Glyceride-Homeostasis in Neuroblastoma Cells and Murine Brain. Biomolecules, 11(11), 1699. https://doi.org/10.3390/biom11111699