Hydroquinone-induced apoptosis of human lymphocytes through caspase 9/3 pathway.
Hydroquinone (HQ) is a major benzene metabolite, which is produced after benzene biotransformation. In this study, we investigated the toxic effect of HQ on lymphocytes. HQ significantly induced the apoptosis of lymphocytes isolated from normal peripheral blood in both dose and time dependent courses. Volatile organic compounds such as benzene, phenol, formaldehyde, o- and p-xylene, and toluene have no effect on lymphocyte apoptosis. HQ induced the cleavage of procaspase 3 and procaspase 9, indicating activation of the pro-apoptotic enzymes. Supernatant was collected from normal lymphocytes after HQ treatment and it significantly induced the apoptosis of normal lymphocytes as compared to supernatant collected from normal lymphocytes without HQ treatment. HQ reduced the secretion of MCP-1, IL-6 and IL-8 increased by in vitro incubation, although benzene and phenol are not effective in cytokine production. HQ increased the intracellular ROS production of lymphocytes. Benzene and phenol also increased the ROS production. In summary, HQ has a cytotoxic effect on lymphocytes by apoptosis induction and the pro-apoptotic signaling is involved in caspase 9/3 pathway. Our results demonstrated that HQ induces apoptosis by activating caspases 9/3 pathway and that the toxic effect seems to be dependent on lymphocyte metabolism.
Department of Clinical Laboratory Science, Wonkwang Health Science University, Iksan, Republic of Korea.
Ji-Sook
JS
Lee
Eun Ju
EJ
Yang
In Sik
IS
Kim
D017209:Apoptosis / Q000187:drug effects*; D001554:Benzene / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism*; D053453:Caspase 9 / Q000378:metabolism*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D003603:Cytotoxins / Q000633:toxicity*; D004789:Enzyme Activation; D006801:Humans; D006873:Hydroquinones / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D019800:Phenol / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
D017077:Culture Media, Conditioned; D016207:Cytokines; D003603:Cytotoxins; D006873:Hydroquinones; D017382:Reactive Oxygen Species; D019800:Phenol; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D001554:Benzene; C031927:hydroquinone