Arecoline-mediated inhibition of AMP-activated protein kinase through reactive oxygen species is required for apoptosis induction.
Oral Oncol
; 47(5): 345-51, 2011 May.
Article
en En
| MEDLINE
| ID: mdl-21440488
Arecoline is the major alkaloid of areca nut (AN) and known to induce reactive oxygen species (ROS) production and apoptosis. The metabolic sensor AMP-activated protein kinase (AMPK), activated by ROS, also regulates apoptosis. This study used several types of cells as the experimental model to analyze the roles of ROS and AMPK in arecoline-induced apoptosis. We found that arecoline dose-dependently increased intracellular ROS level, and two antioxidants, N-acetyl-L-cysteine (NAC) and glutathione, attenuated arecoline-induced apoptotic cell death. Interestingly, arecoline dose- and time-dependently inhibited rather than stimulated AMPK-Thr(172) phosphorylation, and both NAC and glutathione relieved this inhibition. The AMPK activator, 5-aminoimidazole-4-carboxamide 1-ß-D-ribofuranoside (AICAR), also restored the phosphorylation level of AMPK-Thr(172) and attenuated apoptotic cell death under arecoline insult. In contrast, the AMPK inhibitor, compound C, and RNA interference of AMPK expression increased the cytotoxicity of arecoline. Collectively, these results suggest that arecoline may inhibit AMPK through intracellular ROS, responsible for the execution of apoptosis.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Arecolina
/
Especies Reactivas de Oxígeno
/
Apoptosis
/
Proteínas Quinasas Activadas por AMP
Límite:
Humans
Idioma:
En
Revista:
Oral Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2011
Tipo del documento:
Article
Pais de publicación:
Reino Unido