Journal
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
Volume 59, Issue 1, Pages 49-59Publisher
WILEY
DOI: 10.1002/em.22126
Keywords
hydroquinone; B cell leukemia; lymphoma-2; poly(ADP-ribose) polymerase-1; ABT-737; mitochondrial membrane potential; cytoplasmic translocation
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Funding
- Guangdong Provincial Natural Science Foundation, China [S2013010015153]
- Key project of Science and Technology Program of Dongguan Bureau of Science and Technology, China [2012108101011]
- Science and Technology Program of Zhanjiang Bureau of Science and Technology, China [2013B01082]
- Science Foundation of Guangdong Medical University, China [M2013004]
- Key Program of National Natural Science Foundation of China [81430079]
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B cell leukemia/lymphoma-2 (Bcl-2) suppresses apoptosis by binding the BH3 domain of proapoptotic factors and thereby regulating mitochondrial membrane potential (MMP). This study aimed to investigate the role of Bcl-2 in controlling the mitochondrial pathway of apoptosis during hydroquinone (HQ)-induced TK6 cytotoxicity. In this study, HQ, one metabolite of benzene, decreased the MMP in a concentration-dependent manner and induced the generation of reactive oxygen species (ROS), the activation of the DNA damage marker -H2AX, and production of the DNA damage-responsive enzyme poly(ADP-ribose)polymerase-1 (PARP-1). Exposure of TK6 cells to HQ leads to an increase in Bcl-2 and co-localization with PARP-1 in the cytoplasm. Inhibition of Bcl-2 using the BH3 mimetic, ABT-737, suppressed the PARP-1 nuclear to cytoplasm translocation and sensitized TK6 cells to HQ-induced apoptosis through depolarization of the MMP. Western blot analysis indicated that ABT-737 combined with HQ increased the levels of cleaved PARP and -H2AX, but significantly decreased the level of P53. Thus, ABT-737 can influence PARP-1 translocation and induce apoptosis via mitochondria-mediated apoptotic pathway, independently of P53. In addition, we found that knockdown of PARP-1 attenuated the HQ-induced production of cleaved PARP and P53. These results identify Bcl-2 as a protective mediator of HQ-induced apoptosis and show that upregulation of Bcl-2 helps to localize PARP-1 to the cytoplasm and stabilize MMP. Environ. Mol. Mutagen. 59:49-59, 2018. (c) 2017 Wiley Periodicals, Inc.
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