title: Tetrachlorobenzoquinone triggers the cleavage of Bid and promotes the cross-talk of extrinsic and intrinsic apoptotic signalings in pheochromocytoma (PC) 12 cells.
abstract: Although there are few studies suggested PCP exposure induced developmental and behavioral disorders, however, the occurrence of neurotoxicity and PCP has not been firmly established. Tetrachlorobenzoquinone (TCBQ) is a reactive metabolite of environmental pollutant pentachlorophenol (PCP). To the best of our knowledge, there has no information regarding to the neurological toxic effect of TCBQ available. Here, we demonstrated that TCBQ induces cytotoxicity in pheochromocytoma PC12 cell line, and the mode-of-action analysis indicated the involvement of apoptotic signalings, such as the activation of caspase family proteins, the increased expressions of Fas and Fas-associated death domain (FADD), the loss of mitochondrial membrane potential (MMP), the release of cytochrome c (Cyt c) and the cleavage of the caspase substrates poly(ADP-ribose) polymerase (PARP). BI-6C9, a specific BH3-interacting domain death agonist (Bid) inhibitor, repressed TCBQ-induced Bid truncation, along with the activation of caspase 3 and the release of Cyt c, suggested the cross-talk of extrinsic and intrinsic apoptotic signalings. Furthermore, the inhibition of caspase 8 impaired TCBQ-induced the activation of caspase 3, as well as the release of Cyt c and the cleavage of Bid, suggesting caspase 8 acting as the upstream molecule of Bid, and TCBQ-induced apoptosis is initiated via caspase 8, leads to the activation of caspase 9/3 through Bid-mediated amplification loop. Finally, the pretreatment of antioxidant NAC ameliorated Fas, FADD and caspase 8/3 expressions, which illustrated that TCBQ-induced apoptotic signaling is ROS dependent. Taken together, these results indicated that the cleavage of Bid may play an important role in TCBQ-induced neurotoxicity which promotes the cross-talk of extrinsic and intrinsic apoptotic signalings in PC12 cells.
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Beibei, Chongqing 400715, People's Republic of China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Hu
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Beibei, Chongqing 400715, People's Republic of China.
authors.forename: Chuanyang
authors.initials: C
authors.lastname: Su
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Beibei, Chongqing 400715, People's Republic of China.
authors.forename: Xiufang
authors.initials: X
authors.lastname: Song
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Beibei, Chongqing 400715, People's Republic of China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Beibei, Chongqing 400715, People's Republic of China.
authors.forename: Juanli
authors.initials: J
authors.lastname: Fu
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Beibei, Chongqing 400715, People's Republic of China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Xia
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Beibei, Chongqing 400715, People's Republic of China.
authors.forename: Demei
authors.initials: D
authors.lastname: Xu
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Beibei, Chongqing 400715, People's Republic of China.
authors.forename: Erqun
authors.initials: E
authors.lastname: Song
authors.affiliation: Key Laboratory of Luminescence and Real-Time Analytical Chemistry (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Beibei, Chongqing 400715, People's Republic of China. Electronic address: songyangwenrong@hotmail.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism*; D016227:Benzoquinones / Q000494:pharmacology*; D053181:Caspase 8 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D006843:Hydrocarbons, Chlorinated / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D009153:Mutagens / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
chemical_list: D017304:Annexin A5; D051023:BH3 Interacting Domain Death Agonist Protein; D016227:Benzoquinones; C494816:Bid protein, rat; D053200:Fas-Associated Death Domain Protein; D006843:Hydrocarbons, Chlorinated; D009153:Mutagens; C000591600:tetrachlorobenzoquinone; D007770:L-Lactate Dehydrogenase; D053181:Caspase 8
keywords: Apoptosis; Bid; Caspase; Neurotoxicity; ROS; TCBQ