Involvement of the mitochondrion-dependent pathway and oxidative stress in the apoptosis of murine splenocytes induced by areca nut extract.
Areca quid chewing is a major risk factor for oral submucous fibrosis and oral cancer. Clinical evidence suggests that the pathophysiology of the oral diseases is closely associated with immune deterioration. The objective of the present studies was to investigate the pro-apoptotic effect of areca nut extract (ANE) in lymphocytes. Exposure of naïve splenic lymphocytes to ANE significantly enhanced apoptosis in a time- and concentration-dependent manner. Results from Hoechst staining confirmed the morphological features characteristic of apoptosis in ANE-treated cells. ANE treatment induced the depolarization of mitochondrial membrane potential (Deltapsi(m)), which preceded the occurrence of apoptosis. In parallel with the disruption of Deltapsi(m), ANE induced the release of cytochrome c, and the activation of caspase-9, indicating the activation of the mitochondrion-dependent pathway. Moreover, an increased level in the intracellular reactive oxygen species was detected in ANE-treated lymphocytes undergoing apoptosis. ANE-mediated apoptosis, caspase-9 activation and ROS production, but not Deltapsi(m) depolarization, were partially but significantly attenuated in the presence of the antioxidant N-acetyl-L-cysteine (NAC). Collectively, these results demonstrated the pro-apoptotic effect of ANE in primary lymphocytes, which was mediated, at least in part, by the activation of the mitochondrion-dependent pathway and oxidative stress.
Wang
Chia-Chi
CC
Department and Graduate Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan, ROC.
Liu
Tsung-Yun
TY
Cheng
Chiung-Hsiang
CH
Jan
Tong-Rong
TR
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001114:Areca / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009754:Nuts / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000008:administration & dosage / Q000633:toxicity*; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013997:Time Factors
D010936:Plant Extracts