title: Effect of GADD45a on olaquindox-induced apoptosis in human hepatoma G2 cells: Involvement of mitochondrial dysfunction.
abstract: Olaquindox, a quinoxaline 1, 4-dioxide derivative, has been widely used as a feed additive for promoting animal growth in China. The aim of present study was to investigate the effect of grow arrest and DNA damage 45 alpha (GADD45a) on olaquindox-induced apoptosis in HepG2 cells. The result showed that olaquindox induced the decrease of cell viability in a dose dependent manner. Compared to the control group, olaquindox treatment at 400 and 800μg/mL increased the expression level of GADD45a protein and reactive oxygen species (ROS) production, decreased mitochondrial membrane potential (MMP), and subsequently increased the expression of Bax while decreased the expression of Bcl-2, leading to the release of cytochrome c (Cyt c). However, knockdown of GADD45a enhanced olaquindox-induced ROS production, disrupted MMP and subsequently caused Cyt c release, then further increased olaquindox- induced cell apoptosis by increasing the activities of caspase-9, caspase-3, and poly (ADP-ribose) polymerase (PARP). In conclusion, the results revealed that GADD45a played a critical role in olaquindox-induced apoptosis in HepG2 cells, which may embrace the regulatory ability on the mitochondrial apoptosis pathway.
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No. 2, Haidian District, Beijing, PR China.
authors.forename: Daowen
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No. 2, Haidian District, Beijing, PR China.
authors.forename: Chongshan
authors.initials: C
authors.lastname: Dai
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No. 2, Haidian District, Beijing, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No. 2, Haidian District, Beijing, PR China.
authors.forename: Xiayun
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No. 2, Haidian District, Beijing, PR China.
authors.forename: Kena
authors.initials: K
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No. 2, Haidian District, Beijing, PR China.
authors.forename: Xilong
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Yuanmingyuan West Road No. 2, Haidian District, Beijing, PR China. Electronic address: tssfj@163.com.
authors.forename: Shusheng
authors.initials: S
authors.lastname: Tang
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D055785:Gene Knockdown Techniques; D056945:Hep G2 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011810:Quinoxalines / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000097642:GADD45 Proteins
chemical_list: D053148:Caspase 3; D053453:Caspase 9; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D011065:Poly(ADP-ribose) Polymerases; D011810:Quinoxalines; D017382:Reactive Oxygen Species; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C013168:olaquindox
keywords: Apoptosis; GADD45a; Mitochondrial dysfunction; Olaquindox; ROS