Protective effect of S-allyl- l-cysteine, a garlic compound, on amyloid β-protein-induced cell death in nerve growth factor-differentiated PC12 cells

Abstract

Aged garlic extract (AGE) contains several neuroactive compounds, including S-allyl- l-cysteine (SAC) and allixin. We characterized cell death induced by amyloid β-protein (Aβ), 4-hydroxynonenal (HNE), tunicamycin, an endoplasmic reticulum (ER) stressor, or trophic factor deprivation, and investigated whether and how SAC could prevent this in nerve growth factor (NGF)-differentiated PC12 cells, a model of neuronal cells. Exposure of the cells to amyloid β-protein 1–40 (Aβ 1–40) decreased the extent of [3-(4,5)-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT) reduction activity and loss of neuronal integrity, but these effects were not prevented by Ac-DEVD-CHO, a caspase-3 inhibitor. Simultaneously applied SAC protected the cells against Aβ-induced cell death in a concentration-dependent manner. It also protected them against tunicamycin-induced neuronal death. In contrast, it afforded no protection against cell death induced by HNE and trophic factor deprivation, which is mediated by a caspase-3-dependent pathway. These results suggest that SAC may selectively protect cell death induced by Aβ and tunicamycin, which may be triggered by ER dysfunction in NGF-differentiated PC12 cells.