Table 1. Levels of ceramides, cholesterol, and oxidative stress are increased in neurons exposed to Aβ1–42, and α-tocopherol and an inhibitor of sphingolipid synthesis attenuates these effects of Aβ1–42.
Compound | Control | 5 μM Aβ | 100 nM ISP-1 | 100 nM ISP-1 plus 5 μM Aβ | 50 ug/ml α-tocopherol | 50 ug/ml α-tocopherol plus 5 μM Aβ |
---|---|---|---|---|---|---|
SM C18:0 | 182 ± 21 | 190 ± 11 | 143 ± 13 | 151 ± 20 | 176 ± 17 | 196 ± 22 |
SM C24:0 | 69.4 ± 7.8 | 12.6 ± 2.8†† | 57.5 ± 1.2** | 66.5 ± 8.5** | 64.3 ± 4.3** | 58.2 ± 5.5** |
Cer C18:0 | 20.0 ± 1.4 | 39.6 ± 2.1†† | 23.4 ± 4.1* | 18.7 ± 1.3** | 18.1 ± 4.7** | 22.9 ± 4.0* |
Cer C24:0 | 0.95 ± 0.05 | 2.40 ± 0.21†† | 1.65 ± 0.20† | 0.85 ± 0.13** | 0.63 ± 0.09** | 0.90 ± 0.10** |
Gal-cer C24:0 | 0.13 ± 0.02 | 0.20 ± 0.02† | 0.11 ± 0.01** | 0.13 ± 0.02** | 0.11 ± 0.09** | 0.15 ± 0.07* |
Cholesterol | 50.4 ± 14.0 | 124.1 ± 13.5†† | 43.9 ± 10.0** | 71.7 ± 13.5* | 8.6 ± 4.1††** | 16.2 ± 5.5††** |
Chol-ester C18:1 | 2.10 ± 0.31 | 3.30 ± 0.25 | 1.65 ± 0.29** | 0.90 ± 0.03††** | 2.33 ± 0.25 | 2.13 ± 0.51 |
4HNE | 0.19 ± 0.04 | 1.20 ± 0.28† | 0.21 ± 0.07** | 0.23 ± 0.06** | 0.03 ± 0.02††** | 0.06 ± 0.02††** |
Cultured hippocampal neurons were pretreated for 24 h with 50 ug/ml α-tocopherol or for 30 min with either 100 nM ISP-1 or vehicle, and were then exposed for 6 h to 5 uM Aβ1-42 or saline (control) and levels of sphingomyelins, ceramides, cholesterols, and HNE were quantified. The values of HNE represent the sum of free, lysine-HNE (2-pentylpyrrole), and histidine-HNE adducts. Values (cps/total phospholipids × 106) are the mean and SE of determinations made in three separate cultures. †, P < 0.05; ††, P < 0.01 compared with the control value. *, P < 0.05; **, P < 0.01 compared with the value for cultures exposed to Aβ alone. SM, sphingomyelin; Cer, ceramide.