N-acetyl cysteine protects human oral keratinocytes from Bis-GMA-induced apoptosis and cell cycle arrest by inhibiting reactive oxygen species-mediated mitochondrial dysfunction and the PI3K/Akt pathway.
Bisphenol-A-glycidyl methacrylate (Bis-GMA) released from dental resin materials causes various toxic effects on gingival epithelium. Thus the underlying mechanisms of its cytotoxicity should be elucidated for safety use. One potential cause of cell damage is the generation of reactive oxygen species (ROS) beyond the capacity of a balanced redox regulation. In this study, we found that exposure of human oral keratinocytes (HOKs) to Bis-GMA caused apoptosis and G1/S cell cycle arrest in parallel with an increased ROS level. Moreover, Bis-GMA induced a depletion of mitochondrial membrane potential, an increase in the Bax/Bcl-2 ratio, an activation of caspase-3 and altered expressions of cell cycle-related proteins (p21, PCNA, cyclinD1). Furthermore, the co-treatment of the ROS scavenger N-acetyl cysteine (NAC) obviously attenuated Bis-GMA-induced toxicity. Here we also evaluated the effects of Bis-GMA on the ROS-related PI3k/Akt pathway. We found that Bis-GMA inhibited the phosphorylation of Akt, whereas the amount of phosphorylated Akt was reverted to the control level in the presence of NAC. Our findings suggested that the toxic effects of Bis-GMA were related to ROS production and the antioxidant NAC effectively reduced Bis-GMA-mediated cytotoxicity.
Department of Oral and Maxillo-facial Implantology, Shanghai Ninth People's Hospital, School of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Yu
Y
Zhu
Department of Oral and Maxillo-facial Implantology, Shanghai Ninth People's Hospital, School of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Ying-xin
YX
Gu
Department of Oral and Maxillo-facial Implantology, Shanghai Ninth People's Hospital, School of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Jia-ji
JJ
Mo
Department of Oral and Maxillo-facial Implantology, Shanghai Ninth People's Hospital, School of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Jun-yu
JY
Shi
Department of Oral and Maxillo-facial Implantology, Shanghai Ninth People's Hospital, School of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Shi-chong
SC
Qiao
Department of Oral and Maxillo-facial Implantology, Shanghai Ninth People's Hospital, School of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. Electronic address: lhc9@hotmail.com.
Hong-chang
HC
Lai
D000111:Acetylcysteine / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D017438:Bisphenol A-Glycidyl Methacrylate / Q000633:toxicity*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012117:Resins, Synthetic / Q000633:toxicity; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D012117:Resins, Synthetic; D051028:bcl-2-Associated X Protein; D017438:Bisphenol A-Glycidyl Methacrylate; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D000111:Acetylcysteine
Bisphenol-A-glycidyl methacrylate; Cytotoxicity; N-acetyl cysteine; PI3K/Akt; ROS