title: Role of poly(ADP-ribose) glycohydrolase in the regulation of cell fate in response to benzo(a)pyrene.
abstract: Poly(ADP-ribosyl)ation is a crucial regulator of cell fate in response to genotoxic stress. Poly(ADP-ribosyl)ation plays important roles in multiple cellular processes, including DNA repair, chromosomal stability, chromatin function, apoptosis, and transcriptional regulation. Poly(ADP-ribose) (PAR) degradation is carried out mainly by poly(ADP-ribose) glycohydrolase (PARG) enzymes. Benzo(a)pyrene (BaP) is a known human carcinogen. Previous studies in our laboratory demonstrated that exposure to BaP caused a concentration-dependent DNA damage in human bronchial epithelial (16HBE) cells. The role of PARG in the regulation of DNA damage induced by BaP is still unclear. To gain insight into the function of PARG and PAR in response to BaP, we used lentiviral gene silencing to generate 16HBE cell lines with stably suppressed PARG, and determined parameters of cell death and cell cycle following BaP exposure. We found that PARG was partially dependent on PAR synthesis, PARG depletion led to PAR accumulation. BaP-induced cell death was regulated by PARG, the absence of which was beneficial for undamaged cells. Our results further suggested that PARG probably has influence on ATM/p53 pathway and metabolic activation of BaP. Experimental evidences provided from this study suggest significant preventive properties of PAR accumulation in the toxicity caused by BaP.
authors.affiliation: Department of Preventive Medicine, School of Public Health, Sun Yat-sen University, Guangzhou, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Huang
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Cai
authors.forename: Qing-Cheng
authors.initials: QC
authors.lastname: Liu
authors.forename: Gong-Hua
authors.initials: GH
authors.lastname: Hu
authors.forename: Bo
authors.initials: B
authors.lastname: Xia
authors.forename: Ji-Yan
authors.initials: JY
authors.lastname: Mao
authors.forename: De-Sheng
authors.initials: DS
authors.lastname: Wu
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Liu
authors.forename: Zhi-Xiong
authors.initials: ZX
authors.lastname: Zhuang
mesh_terms: D017209:Apoptosis; D064007:Ataxia Telangiectasia Mutated Proteins; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D042822:Genomic Instability; D006026:Glycoside Hydrolases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009153:Mutagens / Q000494:pharmacology*; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009153:Mutagens; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D011064:Poly Adenosine Diphosphate Ribose; D001564:Benzo(a)pyrene; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase