Table 1.
Modulators of APP processing in endothelial cells
| APP Processing Enzymes and Products |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Effectors/Stimuli | Cell Types | APP | Aβ | Mixed sAPPα/β | sAPPα | sAPPβ | α-secretase | β-secretase | Molecular Mechanisms | References |
| Nitric oxide | HBMEC | ↓ | ↓ | ↓ | eNOS/cGMP activation | 7, 8 | ||||
| Iloprost | HBMEC | ↑ | ↔ | ↑ | ↑ | ↔ | Via cAMP and PPARδ activation | 78 | ||
| Cicaprost, forskolin | HBMEC | ↑ | ↑ | cAMP activation | 78 | |||||
| GW501516 | HBMEC | ↔ | ↑ | ↑ | ↔ | SIRT1 activation | 78 | |||
| Thrombin | HUVEC | ↑ | PKC activation | 31 | ||||||
| Interleukin-1 | HBMEC, MBEC, HUVEC | ↑ | ↑ | Increased APP mRNA via PKC activation | 20, 61, 66, 95 | |||||
| Glucose | HUVEC | ↑ | ↑ | ? | 26 | |||||
| TNF-α | MBEC | ↓ (intra-cellular) | Decreased mRNA and protein synthesis of cellular prion protein | 196 | ||||||
| Heat shock | HUVEC | ↑ | Increased mRNA and protein synthesis | 30 | ||||||
| Oxygen-glucose deprivation | RBMEC | ↑ | ↑ | ↑ | Via hypoxia inducible factor-1 | 16, 17 | ||||
| Hypoxia | MBEC | ↑ | ↑ | ↑ | ↑↑ | Increased protein synthesis of APP | 126 | |||
HBMEC, human brain microvessel endothelial cells; HUVEC, human umbilical vein endothelial cells; MBEC, mouse brain endothelial cell line; RBMEC, rat brain microvessel endothelial cells; GW501516, peroxisome proliferator-activated receptors δ (PPARδ) agonist; eNOS, endothelial nitric oxide synthase; cGMP, cyclic guanosine 3′,5′-monophosphate; cAMP, cyclic adenosine 3′,5′-monophosphate; SIRT1, sirtuin 1; PKC, protein kinase C; TNF-α, tumor necrosis factor-α; ↑, upregulation; ↓, downregulation; ↔, no effect.
Blank fields in this table represent that this parameter was not tested. No data are available regarding the effects of effectors/stimuli on APP-processing products AICD and p3 in endothelial cells.