Protective effect of S-allyl-L-cysteine, a garlic compound, on amyloid beta-protein-induced cell death in nerve growth factor-differentiated PC12 cells.
Aged garlic extract (AGE) contains several neuroactive compounds, including S-allyl-L-cysteine (SAC) and allixin. We characterized cell death induced by amyloid beta-protein (Abeta), 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 beta-protein(1-40) (Abeta(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 Abeta-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 Abeta and tunicamycin, which may be triggered by ER dysfunction in NGF-differentiated PC12 cells.
Ito
Yoshihisa
Y
Department of Pharmacology, College of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan. yoshiito@pha.nihon-u.ac.jp
Kosuge
Yasuhiro
Y
Sakikubo
Taeko
T
Horie
Kayo
K
Ishikawa
Natsue
N
Obokata
Naoya
N
Yokoyama
Eiko
E
Yamashina
Kumiko
K
Yamamoto
Machiko
M
Saito
Hiroshi
H
Arakawa
Motoki
M
Ishige
Kumiko
K
D000447:Aldehydes / Q000633:toxicity; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000633:toxicity; D004721:Endoplasmic Reticulum / Q000502:physiology; D005737:Garlic; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009842:Oligopeptides / Q000633:toxicity; D016716:PC12 Cells; D051381:Rats; D014415:Tunicamycin / Q000633:toxicity
D000447:Aldehydes; D016229:Amyloid beta-Peptides; D000900:Anti-Bacterial Agents; D015853:Cysteine Proteinase Inhibitors; D018696:Neuroprotective Agents; D009842:Oligopeptides; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; D014415:Tunicamycin; C065299:S-allylcysteine; D020932:Nerve Growth Factor; C027576:4-hydroxy-2-nonenal; D003545:Cysteine