Altered protein expressions in chronic PCB-153-induced human liver (HepG2) cells.
Polychlorinated biphenyls (PCBs) are a group of persistent and widely distributed environmental pollutants that have various deleterious effects, e.g., neurotoxic, endocrine disruption and reproductive abnormalities, including cancers. Chronic exposure to environmentally hazardous chemicals like PCBs is of great concern to human health. It has been reported earlier that apoptotic proteins change in rats under chronic PCB treatment. It is of importance to determine if chronically exposed human cells develop a different protein expression. In the present study, the authors chronically exposed metabolically competent human liver (HepG2) cells at 50 to 100 microM to examine the role of the well-known environmentally hazardous pollutant non-coplanar 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) to study cell death. After 12 weeks of exposure these cells showed significant changes in apoptotic death in subsequent trypan blue growth assay, fluorescence microscopy, DNA fragmentation, and immunoblotting studies. Interestingly, chronically exposed cells showed marked differences in apoptotic and/or death-related proteins (e.g., Bcl2, Bak, and the pro and active forms of caspase-9, which were up-regulated), in contrast to acutely exposed (i.e., 48-h PCB-153 exposed) cells, which maintained linear growth despite repeated exposures. Similarly, tumor suppressor protein p53, proto-oncogene c-myc, and cell cycle regulator protein p21 were also up-regulated compared to nonchronically exposed HepG2 Cells. The results indicated that PCB-153-induced chronic exposure significantly altered different apoptotic (e.g., Bcl2, Bak, caspase-3) and tumor suppressor (e.g., p21, p53, and c-myc) proteins in the cellular model. These results suggest that chronic exposure to PCB-153 can induce cell survival by altering several apoptotic and tumor suppressor proteins.
Ghosh
Somiranjan
S
Department of Biology, Howard University, Washington, DC, USA.
De
Supriyo
S
Dutta
Sisir K
SK
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D015151:Immunoblotting; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D014176:Protein Biosynthesis / Q000187:drug effects*; D000090063:Proto-Oncogene Mas; D013997:Time Factors
D004785:Environmental Pollutants; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011078:Polychlorinated Biphenyls; C014024:2,4,5,2',4',5'-hexachlorobiphenyl