Study On The Mitochondrial-Dependent Pathway Of Polychlorinated Biphenyls Quinones Induce Apoptosis In HepG2Cells

Polychlorinated biphenyls (PCBs) are synthetic compounds, they have been mass produced and widely used since the1930s because of their characters of chemical stability and insulating properties, thermal stability, flame resistance, thermal conductivity. However, PCBs also have the properties such as recalcitrance, toxicity, bioaccumulation, long-range transport which are the typical characteristics of persistent organic pollutants, so they could result in global contamination of air, water and soil, and they present continuing threat to human health. Consequently, PCBs were one of the12categories of persistent organic pollutants that prohibited use in the Stockholm Convention signed by the United Nations Environment Programme in2001.In recent years, the toxic effects of PCBs and their metabolites have been well elucidated in many studies, and it is showed that they could cause serious harm to the organism, including reproductive toxicity, immunotoxicity, neurotoxicity, skin toxicity, even carcinogenic under conditions that in long-term low-doses or short-term high-dose exposured to PCBs and their metabolites. However, the specific mechanism of the toxic effects is not yet clear. Recent studies have shown that the metabolites of PCBs can cause oxidative damage and inhibit the cell proliferation, showing more serious biological toxic effects than its parent structure. The inhibitory effect of PCBs on cell proliferation, suggesting us that apoptosis may play an important role in their toxicity.Apoptosis is an active process, and it is the programmed cell death of cells respond to external stimuli signal or palliative injury. The regulations of apoptosis are complex and rigorous, including three important pathways:the death receptor pathway, the mitochondria-dependent pathway and endoplasmic reticulum pathways. According to the study of literatures, we suppose that mitochondrial pathway may play a major role in the PCBs quinone induced apoptosis. But it is not clear that how PCBs metabolites cause mitochondrial dysfunction and which regulatory proteins involved in the mitochondrial pathway. Simultaneously, whether it cause the changes of the cell cycle and the contact between apoptosis and cell cycle remains to be investigated.Insummary, our study used HepG2cells cultured in vitro, to verify whether the PCB quinone induce apoptosis. Based on this, according to the known mechanism mode of apoptosis, we gradually speculated the key apoptosis regulatory proteins may be involved in up-stream and down-stream mitochondria pathway, and confirmed with series of experiments. Eventually, we construct a complete pathway of PCBs quinone induced mitochondria-dependent apoptosis signal transduction pathways. At the same time, we detected the change of the cell cycle to have a more in-depth understanding of the mechanism of apoptosis caused by PCBs quinone.Through our study, we can further improve the cytotoxicity mechanism of PCBs, and provide important theoretical basis for elucidating the molecular mechanism of PCBs quinone induced apoptosis, and thus provide new ideas to the treatment and prevention of diseases caused by PCBs.