Regulation of apolipoprotein A-I gene expression by the histamine H1 receptor: Requirement for NF-κB

Publication date: 1 September 2018Source: Life Sciences, Volume 208Author(s): Michael J. Haas, Marilu Jurado-Flores, Ramadan Hammoud, Gabriela Plazarte, Luisa Onstead-Haas, Norman C.W. Wong, Arshag D. MooradianAbstractAimsEarlier it had been found by us that apolipoprotein A-I (apo A-I) is suppressed by histamine in HepG2 cells. Histamine has been shown to regulate NF-κB activity, though not in hepatocytes. Therefore we examined the role of the histamine receptors and NF-κB in histamine-mediated apo A-I gene expression in HepG2 liver cells.Main methodsThe effect of histamine on histamine H1 receptor expression, and NF-κB p65 and p50 subunits was examined by Western blot. Histamine H1 receptor involvement was examined by loss-of-function (via siRNA) and gain-of-function studies overexpressing the histamine H1 receptor. The requirement for the p65 subunit of NF-κB for histamines effect was elucidated by loss-of-function studies (siRNA). Finally, the effect of histamine on NF-κB binding to the apo A-I gene promoter was examined by chromatin immunoprecipitation.Key findingsTreatment of HepG2 cells with histamine had no effect on histamine H1 receptor expression. However, treatment with histamine increased NF-κB p65 and p50 subunit expression significantly. At low levels, the exogenous histamine H1 receptor plasmid suppressed apo A-I gene promoter activity while addition of higher levels of plasmid DNA actually increased apo A-I gene promoter activity. Inhibition of NF-κB a...

Source: Life Sciences - July 19, 2018 Category: Biology Source Type: research