1. Introduction
2. Results and Discussion
2.1. Effect of FA Carbon Chain Length on α-Secretase Activity
2.2. Variations in the Phospholipid Headgroup on α-Secretase Activity
2.3. Effect of FA Saturation on α-Secretase Activity
2.4. Effect of the Double-Bond Position on α-Secretase Activity
3. Experimental Section
3.1. Chemicals and Reagents
3.2. Cell Culture and Incubation with Phospholipids
3.3. Detection of α-Secretase Activity in Vivo
3.4. Human Post Mortem Brains
3.5. Preparation of Purified Membranes
3.6. Preparation of Human Brain Lipid Extract
3.7. Determination of α-Secretase Activity and in Vitro Incubation
3.8. Determination of ADAM10 Purified Enzyme Activity
3.9. Detection of Phospholipid Species in SH-SY5Ywt Cells and Human Post Mortem Brains
3.10. Mass Spectrometry Analysis
3.11. Statistical Analysis
4. Conclusions
Supplementary Information
ijms-14-05879-s001.pdfAcknowledgments
Conflict of Interest
References
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SH-SY5Y membranes | living SH-SY5Y cells | purified ADAM10 | human post mortem brain | |
---|---|---|---|---|
Mean % (SEM % +/− Sign.) | Mean % (SEM % +/− Sign.) | Mean % (SEM % +/− Sign.) | Mean % (SEM % +/− Sign.) | |
Effect of chain length | ||||
PC 10:0 | 127.7 (2.2 n.s.) | 124.8 (1.3 ***) | ||
PC 12:0 | 144.0 (9.3 **) | 126.9 (1.3 ***) | 132.0 (9.6 *) | 141.9 (7.6 **) |
PC 14:0 | 128.0 (11.9 n.s.) | 103.5 (1.2 n.s.) | ||
PC 16:0 | 99.8 (5.9 n.s.) | 99.2 (1.3 n.s.) | ||
PC 18:0 | 100.0 (3.2) | 100.0 (2.3 n.s.) | 100.0 (6.4) | 100.0 (5.7) |
PC 20:0 | 102.3 (0.5 n.s.) | 98.8 (1.9 n.s.) | ||
PC 22:0 | 98.8 (1.9 n.s.) | 100.1 (2.3 n.s.) | ||
PC 24:0 | 101.7 (1.5 n.s.) | 107.8 (2.2 n.s.) | ||
Mean % (SEM % +/− Sign.) | Mean % (SEM % +/− Sign.) | Mean % (SEM % +/− Sign.) | Mean % (SEM % +/− Sign.) | |
Effect of headgroup | ||||
PC 12:0 | 100.0 (0.7) | 100.0 (1.1) | 100.0 (4.5) | |
PE 12:0 | 98.5 (1.3 n.s.) | 93.6 (2.8 n.s.) | 109.2 (3.1 n.s.) | |
PS 12:0 | 93.4 (2.5 n.s.) | 83.8 (1.6 **) | 104.9 (3.7 n.s.) | |
PC 14:0 | 100.0 (1.9) | 100.0 (1.1) | 100.0 (10.9) | |
PE 14:0 | 101.0 (1.5 n.s.) | 105.0 (4.0 n.s.) | 105.7 (3.6 n.s.) | |
PS 14:0 | 116.2 (3.1 ***) | 96.6 (2.0 n.s.) | 104.7 (12.2 n.s.) | |
Mean % (SEM % +/− Sign.) | Mean % (SEM % +/− Sign.) | Mean % (SEM % +/− Sign.) | Mean % (SEM % +/− Sign.) | |
Effect of saturation | ||||
PC 18:0 | 100.0 (1.2) | 100.0 (2.3) | 100.0 (4.8) | 100.0 (3.1) |
PC 18:1 | 102.0 (1.5 n.s.) | 110.3 (4.3 n.s.) | ||
PC 18:2 | 97.1 (2.1 n.s.) | 115.0 (6.6 n.s.) | ||
PC 18:3 | 98.2 (2.0 n.s.) | 117.4 (2.3 n.s.) | 148.2 (4.2 ***) | 106.3 (2.7 n.s.) |
PC 20:4 | 104.2 (4.8 n.s.) | 124.7 (2.0 **) | ||
PC 20:5 | 123.1 (7.6 **) | 140.1 (14.2 ***) | ||
PC 22:6 | 108.6 (2.6 n.s.) | 136.8 (2.2 ***) | 229.7 (2.7 ***) | 152.0 (17.4 **) |
Mean % (SEM % +/− Sign.) | Mean % (SEM % +/− Sign.) | Mean % (SEM % +/− Sign.) | Mean % (SEM % +/− Sign.) | |
Effect of double-bond position | ||||
PC 18:1D9 | 100.0 (1.8) | 100.0 (4.4) | ||
PC 18:1D6 | 106.1 (1.0 *) | 101.7 (4.5 n.s.) |
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