High levels of homocysteine downregulate apolipoprotein E expression via nuclear factor kappa B

Figure 3 MEK1/2 is a downstream effector of Hcy action on apolipoprotein E promoter in HEK-293 cells. Transient transfections in HEK-293 cells were performed using plasmids containing apoE proximal promoter (-500/+73 region) in the presence or in the absence of homocysteine alone or in combination with U0126 (a MEK inhibitor), or MEK1 expression vectors. Hcy treatment as well as MEK1 overexpression significantly decreased (P < 0.05) the activity of (-500/+73) apoE-luc construct, as compared to the control. The decreased activity of the reporter luciferase gene driven by the apoE proximal promoter (-500/+73) in the presence of 500 μmol/L homocysteine was partially restored by 10 μmol/L U0126 (^bP < 0.01). MEK1/2: MAPK/ERK kinase; Hcy: Homocysteine; ApoE: Apolipoprotein E.