Acrylonitrile induced apoptosis via oxidative stress in neuroblastoma SH-SY5Y cell.
Acrylonitrile (ACN) is a chemical that is widely used in the production of plastics, acrylic fibers, synthetic rubbers and resins. It has been reported that ACN can cause oxidative stress, a condition which is well recognized as an apoptotic initiator; however, information regarding ACN-induced apoptosis is limited. This present study investigated whether ACN induces apoptosis in human neuroblastoma SH-SY5Y cells, and whether its apoptotic induction involves oxidative stress. The results showed that ACN caused activation of caspase-3, a key enzyme involved in apoptosis, in a dose- and time-dependent manner. Detection of sub-G1 apoptotic cell death and apoptotic nuclear condensation revealed that ACN caused an increase in the number of apoptotic cells indicating ACN induces apoptosis in SH-SY5Y cells. ACN dose- and time-dependently increased the level of proapoptotic protein, Bax. Pretreatment with N-acetylcysteine (NAC), an antioxidant, attenuated caspase-3 activation by ACN, as evidenced by a reduction in proteolysis of PARP, a known caspase-3 substrate, as well as in the number of sub-G1 apoptotic cells. Moreover, induction of Bax by ACN was abolished by NAC. Taken together, the results indicate that ACN induces apoptosis in SH-SY5Y cells via a mechanism involving generation of oxidative stress-mediated Bax induction.
Watcharasit
Piyajit
P
Laboratory of Pharmacology, Chulabhorn Research Institute, 54 Moo 4 Vibhavadee-Rangsit Highway, Bangkok 10210, Thailand.
Suntararuks
Sumitra
S
Visitnonthachai
Daranee
D
Thiantanawat
Apinya
A
Satayavivad
Jutamaad
J
D000111:Acetylcysteine / Q000494:pharmacology; D000181:Acrylonitrile / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3 / Q000032:analysis / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D004789:Enzyme Activation; D006801:Humans; D009447:Neuroblastoma; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000378:metabolism
D000975:Antioxidants; D051028:bcl-2-Associated X Protein; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D000181:Acrylonitrile; D000111:Acetylcysteine