Its liver-specific expression in hepatocytes is strongly controlled by hepatocyte nuclear factor-4 alpha (HNF4 alpha). HNF4 alpha expression and transcriptional activity have been demonstrated to be augmented by glucocorticoid receptor (GR) in human hepatocytes and rodent livers. Methods:
It was examined whether GR activation indirectly induces OCT1 gene expression via HNF4 alpha up-regulation in primary human hepatocytes. We also examined which selleckchem other transcription factors are involved in OCT1 gene expression and whether they are regulated by dexamethasone using qRT-PCR and gene reporter assays. Results: We found that dexamethasone significantly up-regulates OCT1 mRNA and protein in normal primary human hepatocytes, but not in hepatocyte-derived tumor cell lines HepG2 and MZ-Hep1. Consistently, we observed that HNF4 alpha is induced by dexamethasone in primary human hepatocytes, but not in hepatocyte tumor-derived cell lines. Viral transduction of MZ-Hep1 cells with the expression constructs for HNF4 alpha, CCAAT/enhancer binding proteins beta (C/EBP beta) and peroxisome proliferator-activated receptor-gamma coactivator l alpha (PGC1 alpha) demonstrated significant roles of the transcription factors in OCT1 gene regulation. We found that expression of OCT1 mRNA in human livers significantly correlates
with C/EBP beta and HNF4 alpha mRNAs expression and that C/EBP beta co-transfection stimulates
OCT1 gene reporter construct in HepG2 cells. Selleckchem Autophagy inhibitor Nevertheless, neither C/EBP beta nor PGC1 alpha were up-regulated in human SBI-0206965 order hepatocytes by dexamethasone. Conclusion: We can conclude that GR-induced expression of HNF4 alpha may contribute to indirect OCT1 gene up-regulation by dexamethasone in primary human hepatocytes, but not in hepatocyte-derived tumor cell lines.”
“Background: public and patient involvement (PPI) in clinical research is increasingly advocated by funding and regulatory bodies. However, little is known about the views of either academics or members of the public about perceptions of the practical realities of PPI, particularly in relation to ageing research. Objective: to survey current levels of PPI in biomedical and clinical research relating to ageing at one institution. To compare and contrast the views of academics and the public about PPI relating to research about ageing. Design: electronic survey of senior academics, postgraduate students and members of a local user group for older people. Setting and participants: thirty-three academics (18 principal investigators and 15 PhD students) at a biomedical research institution. Fifty-four members of a local user group for older people. Results: thirty per cent (10/33) of projects described some PPI activity. Older adults were more positive about active involvement in research about ageing than academics.