RESUMO
Significant correlations between concentrations of PBDEs and heavy metals were observed in the human body. However, there is a lack of evidence on the linkage between the uptake of heavy metals and PBDEs. This study is the first report on the BDE-47 uptake profile in a human cell line. Hg and As exposures to KERTr (human skin derived keratinocyte) did not significantly (p > 0.05) affect the uptake of BDE47, whereas Pb and Cd significantly (p < 0.05) affected the uptake of BDE-47 in KERTr. The change in Km was minor after exposure to all heavy metals. The maximum transport rate (Vmax) after exposure to Pb (Vmax: 5.23 ± 0.49) and As (Vmax: 4.95 ± 0.60) was significantly increased when compared with the background of the KERTr cell line (Vmax: 4.07 ± 0.35). Real-time RT-PCR indicated that OATP-B, OATP-D, and OATP-E were expressed in the KERTr cell line. The upregulation or downregulation of OATP B and D genes were minor after exposure to heavy metals, but the OATP E gene was upregulated by three to fourfold in KERTr cell line after exposure to Pb an Cd, which may explain the significant increase of uptake of BDE-47 in KERTr after exposures to Pb and Cd. This study indicated that the uptake effects should be considered when performing risk assessment of human exposure to PBDEs and heavy metal.
Assuntos
Éteres Difenil Halogenados/farmacocinética , Queratinócitos/metabolismo , Metais Pesados/farmacocinética , Arsênio/farmacocinética , Cádmio/farmacocinética , Linhagem Celular , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Chumbo/farmacocinética , Mercúrio/farmacocinética , Transportadores de Ânions Orgânicos/genética , Transportadores de Ânions Orgânicos/metabolismoRESUMO
CRC is a common malignant tumor in the gastrointestinal tract, and its incidence has increased significantly in recent years. Several studies revealed that lipid metabolism reprogramming contributed to tumorigenicity and malignancy by interfering with energy production, membrane formation, and signal transduction in cancers. ATGL is a kind of hydroxy fatty acid ester of fatty acid synthase, and its role in tumor remains controversial. We compared levels of adipose triglyceride lipase (ATGL) in human CRC specimens to adjacent specimens. To validate the effect of ATGL on the proliferation ability of CRC, CCK8 assay and clone formation assay were performed. To evaluate whether autophagy process takes part in the effect of ATGL on CRC proliferation, the value of LC3-II/LC3-I was detected by western blot and we blocked the SIRT1 to detect value of LC3-II/LC3-I and p62 via western blot. In the end, we detected the value of SIRT1 in CRC specimens. We found that ATGL showed high expression in CRC and positively correlated with clinical stage, indicating poor prognosis of CRC. Moreover, ATGL significantly promoted tumor cell proliferation in vitro. Mechanistically, ATGL promoted CRC cells proliferation by blocking mTOR signaling pathway and activating autophagy process. Further, ATGL regulated autophagy process through triggering SIRT1 expression. Our results reveal that ATGL promotes colorectal cancer growth by up regulating autophagy process and SIRT1 expression.