Table 1.
Some molecular targets and gene response systems under the influence of α-tocopherol (vitamin E) and its analogues and endogenous metabolites.
| Biological Function | Tocopherol Effect (Up ↑ or Down ↓ Regulation) | Gene Systems | References |
|---|---|---|---|
| Immune-inflammatory response and ferroptotic signaling: |
α-TOH acetate ↓ | NFkB | [20,21] |
| Non-alpha LCMs ↓ (and to a lower extent α-LCMs) |
LOX-5 and COXs | [22,23,24] | |
| α-TOH ↓ (possibly by conversion to α-tocopheryl hydroquinone) | LOX-15 | [25,26,27] | |
| Cholesterol homeostasis | γ-TOH and α-TOH ↑ | PPARγ | [28] |
| α-TOH ↓ | LXR (LXR-regulated receptors: CD36, ABCA1, ABCG1) |
[29] | |
| Lipid metabolism and lipotoxicity-related inflammation |
γ and α-TOH ↑ | PPARα | [30] |
| Garcinoic acid and α-LCMs ↑ | PPARγ | [31,32,33] | |
| Steroidogenesis | α-TOH ↑ | AP-1 and Ref-1 | [34] |
| Platelet aggregation | α-TOH↓ | GP IIb | [35] |
| Xenobiotic detoxification | T3 ↑ LCMs ↑ (particularly δ-T3-13COOH or garcinoic acid) |
PXR (PXR-regulated genes: CYP3A4 Pgp) |
[36,37] |
| Estrogen receptor | T3 ↑ | Erβ (Erβ-regulated genes: MIC-1, ECR-1 and cathepsin D) |
[38] |
Abbreviations: Tocotrienols (T3); Tocopherols (TOH); Long-chain metabolites (LCMs); delta-tocotrienol-13′-carboxy LCM (δ-T3-13′COOH); Nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB); Peroxisome proliferator-activated receptor gamma (PPARγ); Liver X Receptor (LXR); cluster of differentiation 36 (CD36); ATP-binding cassette transporter (ABCA1); ATP-binding cassette G1 transporter (ABCG1); Peroxisome proliferator-activated receptor alpha (PPARα); Activator protein-1 (AP-1); Redox-regulated protein (Ref-1); Glycoprotein IIb (GP IIP); Pregnane X receptor (PXR); Cytochrome P3A4 (CYP3A4); estrogen receptor beta (ERβ); Macrophage inhibitory cytokine 1 (MIC-1); Estrogen receptor 1 (ECR-1).